Peptides sale introduction
Our peptides sale specializes in and covers popular, often scientifically researched perspective peptides, sarms and non-dangerous chemicals in biology and chemistry. If you would like to buy peptides, sarms and other substances of the highest possible quality for scientific research purposes and use, sure you are in the right place.
We are extremely focused about the highest possible quality, this is our top priority. Therefore, in our offer you will find for sale peptides, sarms and other research chemicals of the highest achievable and possible quality, pharmaceutical grade purity and maximum efficiency only. Simultaneously, all our premium peptides, sarms and research chemicals are regularly tested for best quality & purity. The satisfaction of our customers is really important for us, we always try do our maximum for it.
Basic definition what are peptides: Peptides are short chains that consist of two or more (2 to 50) amino acid monomers (molecules), linked together by covalent chemical bonds named peptide bond. Peptides are structurally same as protein, but they are smaller (proteins consist of 50 amino acid molecules or more), and also they do not have secondary and tertiary structures. Human body needs 20 naturally occurring amino acids. These amino acids can be combined into a large number of different peptides and proteins.
The amino acid sequence: Each peptide consists from sequence of amino acids. The amino acid sequence of the peptide is important information, that defines which amino acids have formed the peptide, and in what order they are linked by peptide bond; and this amino acid sequence of a protein or peptide is often referred to as peptide primary structure. Nowadays, scientists know and record complete amino acid sequences of more than 100,000 peptides & proteins, wherein each such peptide or protein has its unique and precisely defined amino acid sequence! The process of determining the amino acid sequence is known as protein sequencing.
There are many peptides discovered and many kinds of peptides are known. Peptides can be sorted, classified or categorized according to many factors or their properties, such as chemical structure & properties, number of amino acids, functions and operation, occurrence, place of action, source, origin and others. These peptides types can often overlap, what means that a particular peptide may fall and belong to several group, categories or types of peptides simultaneously. Examples of important and often used marking of peptide types, kinds, classes, group, categories or families:
Peptide types by number of amino acids (length): Peptides of defined length, according to their number of AA, are named using IUPAC numerical multiplier prefixes:
- di-peptide: is a peptide consisting of 2 amino acids
- tri-peptide: is a peptide consisting of 3 amino acids
- tetra-peptide: is a peptide consisting of 4 amino acids
- penta-peptide: is a peptide consisting of 5 amino acids
- hexa-peptide: is a peptide consisting of 6 amino acids
- hepta-peptide: is a peptide consisting of 7 amino acids
- octa-peptide: is a peptide consisting of 8 amino acids
- nona-peptide: is a peptide consisting of 9 amino acids
- deca-peptide: is a peptide consisting of 10 amino acids
- undeca-peptide: is a peptide consisting of 11 amino acids
- dodeca-peptide: is a peptide consisting of 12 amino acids
- trideca-peptide: is a peptide consisting of 13 amino acids
- tetradeca-peptide: is a peptide consisting of 14 amino acids
- pentadeca-peptide: is a peptide consisting of 15 amino acids
- hexadeca-peptide: is a peptide consisting of 16 amino acids
- heptadeca-peptide: is a peptide consisting of 17 amino acids
- octadeca-peptide: is a peptide consisting of 18 amino acids
- nonadeca-peptide: is a peptide consisting of 19 amino acids
- icosa-peptide: is a peptide consisting of 20 amino acids
- henicosa-peptide: is a peptide consisting of 21 amino acids
- docosa-peptide: is a peptide consisting of 22 amino acids
- tricosa-peptide: is a peptide consisting of 23 amino acids
- tetracosa-peptide: is a peptide consisting of 24 amino acids; etc...
Peptide types & terms that does not have strict length definitions (these types can often overlap):
- polypeptide: single linear peptide chain of many amino acids, held together by amide bonds
- protein: consists of 1 or more polypeptides and simultaneously its total number of amino acids (length) is more than 50 amino acids
- oligopeptide: is a peptide that consists of 2 to 20 amino acids
Peptide types by structure:
- linear peptides: they are peptides that have a structure with simple linear sequence of peptide bonds, chain with a line structure
- cyclic peptides: they are peptides that have a structure with circular sequence of peptide bonds, chains with a ring structure
Main peptide types & classes by functions or occurrence:
- peptide hormones: hormones whose molecules are peptides, peptide hormones are synthesized in cells from amino acids according to mRNA transcripts
- neuropeptides: neuronal signalling molecules, used by neurons to communicate with each other, that influence activity of brain and body in specific ways
- lipopeptides: is a molecule consisting of a lipid connected to a peptide
- peptide proteoses: mixture of peptides produced by the hydrolysis of proteins
- peptidergic agent: chemical which functions to directly modulate the peptide systems in the body or brain
- venom peptides: are usually found in animal venoms, many of which are bioactive
- antimicrobial (antibiotic) peptides (AMPs): represent an important part of innate immune defences in many live organisms
- anticancer peptides ((ACPs): peptides active against microbial and cancer cells, with an efficient tissue penetration and uptake by the heterogeneous cancer cells
- anti-inflammatory peptides (AIPs): are present in all living organisms and does have anti-inflammatory properties
- vaccine peptides: peptides which serves to immunize an organism against a pathogens
- plant peptides: regulates plant growth, development, reproduction and environmental stress responses
- skin peptides: peptides used in skin care, that can provide anti-aging benefits for skin
- cardiovascular peptides: are secreted by the heart in proportion to cardiac transmural pressures
- endocrine peptides: peptides hormones involved in the functioning of the endocrine system
- gastrointestinal peptides: hormones secreted by enteroendocrine cells in stomach, pancreas, and small intestine, controlling functions of the digestive organs
- neurotrophic peptides: peptides that support the growth, survival, and differentiation of developing and mature neurons
- renal peptides: peptides and low molecular weight proteins forming Kidney targeted drug systems
- opioid peptides: bind to opioid receptors in brain, and play role in motivation, emotion, attachment behaviour, response to stress and pain, and control food intake
Peptide types by source and/or origin:
- naturally occurring peptides (naturally produced in human, animal or plant bodies)
- ribosomal peptides: naturally produced peptides in ribosomes (living cell's macromolecular mechanisms)
- non-ribosomal peptides: also naturally produced peptides in living organisms, but synthesized by one or more specialized enzymes
- synthetically designed & manufactured peptides (artificially created by scientists)
- peptide fragments (e.g. hgh fragment) refer to fragments of proteins that are used for example to identify or quantify the source protein
- peptones: peptides and proteins formed in the early stage of protein breakdown during digestion, products of acid proteolysis
Peptides as chains of amino acids held together by peptide bonds (or sometimes by a few isopeptide bonds). A peptide bond is a synonym for term amide bonds, an amide type of covalent chemical bond. Peptide bond is synthesized when the carboxyl group (COOH) of one amino acid molecule reacts with the amino group (NH2) of the other amino acid molecule. The process by which this amide bond is formed proceeds as follows: Two amino acids approach each other, wherein, the non-side chain (C1) carboxylic acid moiety of one amino acid coming near the non-side chain (N2) amino moiety of the second amino acid. One amino acid loses a hydrogen (H) and oxygen (O) from its carboxyl group (COOH), the second amino acid loses a hydrogen (H) from its amino group (NH2), and carbon number one (C1) from carboxyl group of first amino acid is joined with nitrogen number two (N2) from amino group of second amino acid - an amide type of covalent chemical bond (peptide bond) between the residues of these amino acids is created. Simultaneously, a water molecule is formed from released two hydrogen and one oxygen atoms. Therefore, the formation of a peptide bond is a type of condensation reaction. The term residues denotes to amino acids, that have been incorporated and linked into peptides. This chemical reaction (formation of the peptide bond) consumes energy. In live organisms, the necessary energy is derived from ATP.
Structure of Peptides:
As we mentioned earlier, peptides consists from sequence of amino acids joined together by peptide bonds. Two very important facts - which amino acids (their residues) form the peptide, and the order in which they are joined together by peptide bonds (the exact sequence of amino acids), defines its main structure, often called as the primary structure of peptide. All peptides except cyclic peptides, have an N-terminus (on the left end, also known as the amino-terminus, referring to the free amine group (-NH2)), and C-terminus (on the right end, also known as the carboxyl-terminus, referring to the free carboxyl group (-COOH)). And peptides primary structure conventionally begins at the amino-terminus end (on the left), and continues until the carboxyl-terminus end (on the right).
Since the N-terminus of the peptide is different from its C-terminus, even a small peptide may have several constitutional isomers. For example, a dipeptide, formed only from 2 different amino acids may have 2 different structures: Aspartic acid (Asp) and phenylalanine (Phe) may be combined to 2 different dipeptides - Asp-Phe or Phe-Asp. Tripeptide consisting from residues of 3 different amino acids can be created in 6 different constitutions. Tetrapeptide composed from residues of 4 different amino acids would have 24 constitutional isomers, etc. Considering the fact that there are 20 naturally occurring amino acids, and each of which is a possible component of the peptide chain, for example the decapeptide made up from all possible combinations of these amino acids would have total 2010 constitutional isomers!! As we can see, the possible combination of peptide-forming amino acids (peptide amino acid sequences) and unique peptides is truly enormous.. Peptides also often can have posttranslational modifications such as sulfonation, phosphorylation, hydroxylation, palmitoylation, glycosylation or disulfide formation. The amino acids differ in structure by the substituent on their side chains. These aminoacids side-chains provide and affect different chemical, physical and structural properties to the final peptide. Depending on amino acid side-chain substituent, can be amino acid classified as acidic, basic or neutral.
Secondary, Tertiary and Quaternary Structure of Large Peptides:
The differ properties of peptides can depend not only on their amino acids sequences, but in case of large peptides, also on their three dimensional arrangements and on the way in which the peptides chains are stretched, coiled and folded in space. Although the orientational possibilities of these macromolecules may seem almost endless, several factors limit the structural options, and it is possible to identify some common structural themes or secondary peptide structures that appear repeatedly in different molecules. These conformational segments are sometimes described by the dihedral angles Φ & Ψ. But most large peptides and proteins do not adopt completely uniform conformations. Therefore full descriptions of their three dimensional arrangements are defined as another tertiary peptide structures. Quaternary structure only applies to proteins that are composed of more than one polypeptide chain. Each of the polypeptides is called a subunit.
List of factors, that influence the conformational equilibria of peptide chains:
- The planarity of peptide bonds and conformations are defined by dihedral angles Φ and Ψ
- Hydrogen bonding of amide carbonyl groups to N-H donors
- Steric crowding of neighboring groups
- Repulsion and attraction of charged groups
- The hydrophilic and hydrophobic character of the substituent groups
The secondary structure of peptides contains 2 its major types:
The α-helix (alpha helix) is a right hand-helix conformation in which every backbone N−H group donates a hydrogen bond to the backbone C=O group of the amino acid located three or four residues earlier along the protein sequence. The hydrogen bonds does this structure very stable.
The β-sheets (beta sheets) consist of β-strands connected laterally by at least 2 or 3 backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation.
N-terminus & C-terminus:
The end of the peptide chain with a free α-amino group (-NH2) is named the N-terminus (aliases: amino-terminus, NH2-terminus, N-terminal end). The other, opposite end of the peptide with a free carboxyl group (-COOH) is named the C-terminus (aliases: carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus). By convention, peptide amino acids sequences are written from left from N-terminus, to right to C-terminus, in LTR (left-to-right) languages. This correlates the translation direction, because when a peptide is translated from messenger RNA, it is also created from N-terminus to C-terminus - what means, amino acids are added to the carbonyl end.
Cyclic peptides are kind of peptides, which contain a circular sequence of peptide bonds (in other words, polypeptide chains with a ring structure). This ring structure of cyclic peptides can be formed by a covalent bond between:
- the amino and carboxyl ends of the peptide (head-to-tail), example: in cyclosporin
- or a bond connection between the amino end and a side-chain residue (head-to-side-chain), example: in bacitracin
- or the carboxyl end and a side-chain residue (tail-to-side-chain), example: in colistin
- or two residue side-chains (side-chain-to-side-chain), or more complicated arrangements, example: in amanitin
The length of cyclic peptides ranges from 2 to hundreds of amino acid residues. Naturally synthesized cyclic peptides are frequently antimicrobial or toxic type. Cyclic peptides does have tendention to be extremely resistant to the process of digestion, thanks to this property, they are able to survive in the human digestive tract. This advantage can be smart utilized at multiple applications in medicine and molecular biology for design of protein-based drugs which can be used orally, because cyclic peptides can be incorporated with protein domains with medical utility and functions (for example as antibiotics, immunosuppressive agents, etc). Protein domains are parts of protein sequence and tertiary structure (the structural and by functional distinct units of proteins), that can evolve, function, and exist independently of the rest of the protein chain, and usually they are responsible for a particular function or interaction in the overall functional role of protein. In our peptide sale you can buy several cyclic peptides, as melanotan 2 and other.
The role of peptides in nature is very important, they are synthesized in all living organisms, humans, animals and plants. Peptides perform a large number of important tasks and irreplaceable functions in living organisms, play a key role in ongoing biological activities and processes. The human body uses for its functioning a wide variety and range of peptides. Among the most important functions of peptides in living organisms based on their types belong:
- Peptide hormones & endocrine peptides act as hormones, they have an effect on the endocrine system, and carry signals between cells and glands.
- Neuropeptides & brain peptides are neuronal-signalling peptide chains, used by neurons to communicate with each other.
- Opioid peptides bind to opioid receptors in brain, and play role in motivation, emotion, attachment behaviour, response to stress and pain, and control food intake.
- Neurotrophic peptides support the growth, survival, and differentiation of developing and mature neurons.
- Antimicrobial peptides represent an important part of innate immune defences in many live organisms, form part of the variety of antimicrobial agents.
- Anti-inflammatory peptides present in all living organisms and does have anti-inflammatory properties, in multicellular organisms anti-inflammatory peptides constitute an essential part of immune system.
- Cardiovascular peptides are secreted by the heart in proportion to cardiac transmural pressures.
- Gastrointestinal peptides are secreted by enteroendocrine cells in stomach, pancreas, and small intestine, and control functions of the digestive organs.
- Plant peptides regulate plant growth, development, reproduction and environmental stress responses.
- Peptides as structural components, where peptides are building blocks of proteins and protein hormones.
- Peptides as enzymes and biologic catalysts, enzymes speed up metabolic reactions. In he human body is a large amount of enzymes, that are involved in many processes (for example in synthesis of cellular parts, energy production or food digestion).
Hormones does have an effect on the endocrine system of humans and animals. Most hormones can be classified as either amino-acids based hormones (amine, peptide, or protein hormones) or lipids based hormones (steroid hormones). Peptide hormones, like the other peptides, are water-soluble and act on the surface of target cells. Among the most important peptide hormones are, for example, IGF-1 and growth hormone, that you can also find in our peptide sale. Mature peptide hormones travel through the blood to all of the cells in the body, where they interact with specific receptor on the surfaces of their target cells. When a peptide hormone binds to its receptor on the surface of the cell, a second messenger appears in the cytoplasm, which triggers signal transduction leading to the cellular responses. Some peptide hormones also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine mechanism.
Neuropeptides are neuronal-signalling amino acids chains, used by neurons to communicate with each other; and influence the activity of the brain and the body in specific ways. Different neuropeptides are involved in a wide range of brain functions (like analgesia, reward, food intake, metabolism, reproduction, social behaviors, learning, memory, etc). Neuropeptides are related to peptide hormones, and in some cases peptides that function in the periphery as hormones also have neuronal functions as neuropeptides. The main distinction between neuropeptide and peptide hormone has to do with the cell types that release them and respond to the molecule: While neuropeptides are secreted from neuronal cells and signal to neighboring cells (primarily neurons); in contrast, peptide hormones are secreted from neuroendocrine cells and travel through the blood to distant tissues where they evoke a response by binding to their specific receptors. Neuropeptides modulate neuronal communication by acting on cell surface receptors. Many neuropeptides are co-released with other small-molecule neurotransmitters. The human genome contains about 90 genes that encode precursors of neuropeptides.
Opioid peptides bind to opioid receptors in brain, and play role in motivation, emotion, attachment behaviour, response to stress and pain, and control food intake. Opioid peptides are released by post-translational proteolytic cleavage of precursor proteins, and precursors consist from these parts:
- signal sequence that precedes a conserved region of about 50 residues
- variable-length region
- sequence of the neuropeptides themselves
Sequence analysis reveals that the conserved N-terminal region of the precursors contains 6 cysteines, which are probably involved in disulfide bond formation. Probably, this region might be important for neuropeptide processing. Endogenous (naturally in the body produced) opioid peptides are divided into these different families:
- Enkephalins: Pentapeptides involved in regulating nociception in the body; are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors.
- Endorphins: Neuropeptides & peptide hormones, produced by central nervous system & pituitary gland; their principal function is to inhibit the communication of pain signals; they may also produce a feeling of euphoria very similar to that produced by other opioids.
- Dynorphins: These ipioids peptides arise from the precursor protein prodynorphin; they are produced in many different parts of the brain (including the hypothalamus, the striatum, the hippocampus and the spinal cord) and has been shown like a modulator of pain responses.
- Nociceptin: 17-amino acid neuropeptide, endogenous ligand for the nociceptin receptor (NOP, ORL-1), and initiates its function to act on numerous brain activities such as pain sensation and fear learning.
- Endomorphins: Natural opioid neurotransmitters central to pain relief; maintain a variety of functions.
|Opioid peptide||Amino acid sequence||Opioid target receptor|
|Leu-enkephalin||YGGFL||δ-opioid receptor†, μ-opioid receptor†|
|Met-enkephalin||YGGFM||δ-opioid receptor†, μ-opioid receptor†|
|Metorphamide||YGGFMRRV-NH2||δ-opioid receptor, μ-opioid receptor|
|Peptide E||YGGFMRRVGRPEWWMDYQKRYGGFL||μ-opioid receptor, κ-opioid receptor|
|α-Endorphin||YGGFMTSEKSQTPLVT||μ-opioid receptor, unknown affinity for other opioid receptors|
|β-Endorphin||YGGFMTSEKSQTPLVTLFKNAIIKNAYKKGE||μ-opioid receptor'†'‡, δ-opioid receptor†|
|γ-Endorphin||YGGFMTSEKSQTPLVTL||μ-opioid receptor, unknown affinity for other opioid receptors|
|Dynorphin A||YGGFLRRIRPKLKWDNQ||κ-opioid receptor'†'‡|
|Dynorphin A1–8||YGGFLRRI||κ-opioid receptor, μ-opioid receptor (partial agonist at δ-opioid receptor)|
|Dynorphin B||YGGFLRRQFKVVT||κ-opioid receptor|
|Big dynorphin||YGGFLRRIRPKLKWDNQKRYGGFLRRQFKVVT||κ-opioid receptor'†'‡|
|† This symbol next to a receptor indicates that the corresponding peptide is a principal endogenous agonist of the receptor in humans.|
‡ This symbol next to a receptor indicates that the corresponding peptide is the endogenous ligand with the highest known potency for the receptor in humans.
Neurotrophic factors (NTFs), or also marked as neurotrophic peptides, are important biomolecules that support growth, survival, and differentiation of developing and also mature neurons. Most of neurotrophic peptides provide their trophic effects on neurons by signaling through tyrosine kinases, usually a receptor tyrosine kinas (they bind to a low affinity receptor (p75) and to a family of closely related high affinity glycoprotein tyrosine receptor kinases). Neurotrophic peptides have significant role in maintenance of neuronal function throughout entire lifetime: Promote neuronal survival, induce synaptic plasticity, and modulate formation of long-term memories in the mature nervous system. They also promote initial growth and development of neurons in central nervous system and peripheral nervous system, are capable of regrowing damaged neurons, and some neurotrophic peptides are released by target tissue in order to guide growth of developing axon. The three basic / mainly neurotrophic peptide families are:
- Neurotrophins, includes: brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3, neurotrophin-4)
- Neuropoietic cytokines (CNTF family), includes: ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), prolactin, growth hormone, leptin, interferons (interferon-α, interferon-β, and interferon-γ), oncostatin M
- GDNF family, includes: GNDF (Glial cell line-derived neurotrophic factor), artemin, neurturin, and persephin
During development neurotrophic peptides does have key functions in mediating the ability of a target (for example skeletal muscle) of a neuron (for example spinal cord motor neuron) to avoid death of the nerve cell (neuronal survival). Neurotrophic peptides play important role in the quality of life of neurons, regulate growth of neurons, associated metabolic functions such as protein synthesis, and the ability of the neuron to make the neurotransmitters that carry chemical signals which allow the neuron to communicate with other neurons or with other targets (for example muscles, glands, etc.). Neurotrophic peptides are nowadays scientifically studied for use in bioartificial nerve conduits, and as potential and promising drugs for treatment of Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD).
Antimicrobial & Anticancer peptides
Antimicrobial peptides (AMPS; or anytime also marked as host defense peptides (HDPS)), are ribosomally synthesized relatively small (<10 kDa), cationic and amphipathic peptides of variable length, sequence and structure (generally consisting from 12-50 amino acids). These peptides are produced by prokaryotes (a unicellular organism that lacks a membrane-bound nucleus, mitochondria, or any other membrane-bound organelle) and eukaryotes (a unicellular organism whose cells have a nucleus enclosed within membranes), and characterized with strong antimicrobial properties. Antimicrobial peptides are wide spectrum and highly effective antibiotics, and essential component of the innate immune systems of all living organisms, because they does have the ability to kill a wide range of microorganisms, such as bacterias, protozoa, yeast, viruses and fungi. Even transformed or cancerous cells: Antimicrobial peptides are an important component of the natural defences of most living organisms against invading pathogens.
Many natural or synthetic cationic peptides have been reported to show significant anticancer activity with characteristics including the ability to kill target cells rapidly, the broad-spectrum of activity, and very specificity for cancer cells. Compared with classical known cancer treatments (such as chemotherapy or radioactive treatment), anticancer peptides with high specificity against cancer cells may present the way of killing cancer cells while protecting normal cells and helping patients to recover rapidly. Of all the proposed mechanisms, 2 general effects of anticancer peptides against cancer cells were suggested: Cytoplasmic membrane disruption via micellization, or pore formation, and induction of apoptosis. In addition to these effects, some anticancer peptides have been reported to display anticancer activity via different mechanisms.
|Anionic peptides||rich in glutamic and aspartic acids||Maximin H5 from amphibians, Dermcidin from humans|
|Linear cationic α-helical peptides||lack in cysteine||Cecropins, andropin, moricin, ceratotoxin and melittin from insects, Magainin, dermaseptin, bombinin, brevinin-1, esculentins and buforin II from amphibians, CAP18 from rabbits, LL37 from humans|
|Cationic peptide enriched for specific amino acid||rich in proline, arginine, phenylalanine, glycine, tryptophan||abaecin, apidaecins from honeybees, prophenin from pigs, indolicidin from cattle|
|Anionic and cationic peptides that contain cysteine and form disulfide bonds||contain 1~3 disulfide bond||1 bond:brevinins, 2 bonds:protegrin from pig, tachyplesins from horseshoe crabs, 3 bonds:defensins from humans, more than 3:drosomycin in fruit flies|
Most of the known ribosomally synthesized antimicrobial peptides have been identified and studied during the last 20 years. These antimicrobial peptides have been isolated from a wide variety of animals, vertebrates, invertebrates and plants (as from bacteria or fungi). Unlike the majority of conventional antibiotics it seems that antimicrobial peptides frequently destabilize biological membranes (act by disrupting the plasma membrane leading to the lysis of the cell), or in other words attack their target cells by permeabilizing the cell membrane. They does have ability form transmembrane channels, and may also have the ability to enhance immunity by functioning as immunomodulators. The cytoplasmic membrane is a frequent target, but peptides may also interfere with DNA and protein synthesis, protein folding, and cell wall synthesis. The initial contact between the peptide and the target organism is electrostatic, as most bacterial surfaces are anionic, or hydrophobic. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by ‘barrel-stave’, ‘carpet’ or ‘toroidal-pore’ mechanisms. Alternately, they may penetrate into the cell to bind intracellular molecules which are crucial to cell living. Intracellular binding models includes inhibition of cell wall synthesis, alteration of the cytoplasmic membrane, activation of autolysin, inhibition of DNA, RNA, and protein synthesis, and inhibition of certain enzymes. However, in many cases, the exact mechanism of killing is unknown. One emerging technique for the study of such mechanisms is dual polarisation interferometry. In contrast to many conventional antibiotics these peptides appear to be bactericidal instead of bacteriostatic. Moreover, many antimicrobial peptides employ sophisticated and dynamic mechanisms of action to effect rapid and potent activities consistent with their likely roles in antimicrobial host defense.
Anti-inflammatory peptides (AIPs) are important peptides occurring in all living organisms, and a large number of peptides derived from plant, mammals, bacteria or marine organisms show markedly antimicrobial and/or anti-inflammatory effects and properties. In multicellular organisms (including humans), anti-inflammatory peptides form an essential part of their immune system. In addition, numerous natural and synthetic anti-inflammatory peptides are highly effective immunomodulators which can interfere with signal transduction pathways involved in inflammatory cytokine expression; and some anti-inflammatory peptides showed antioxidant properties and could prevent the formation of reactive oxygen species (ROS) implicated in the process of numerous chronic and acute inflammatory disorders. Many endogenous peptides identified during inflammatory responses showed anti-inflammatory activities by inhibiting, reducing, and/or modulating the expression and activity of mediators.
Inﬂammation is part of the regular host reaction to injury or infection, that can be caused by toxic factors, pathogens, dam-aged cells, irritants, or allergens. The immune and inflammatory response of human is modulated through a notably complex system of factors. The increase in the blood flow and in the permeability of blood capillaries induces the movement of large molecules, like leukocytes, antibodies, cytokines, oxidants, chemokines, matrix metalloproteinases and complement from the circulation to sites of injury, infection, or immune reaction. The higher blood flow and plasma extravasation into the inflammatory site leads to heat, redness, swelling, and can causes also pain.
The inflammatory process is the first step of the immunologic response to toxins, invading pathogens and allergens, as well as to damaged tissue; and is a physiological mechanism used by living organisms to defend themselves against infection, restoring homeostasis in damaged tissues. But inflammation also represents the starting point of several chronic diseases such as asthma, skin disorders, cancer, cardiovascular syndrome, arthritis, and neurological diseases. Immunological, microbiological, and toxic factors may induce inflammatory reactions by stimulating various kinds of cellular and humoral components. The inflammatory reactions triggered by inflammatory stimuli such as pathogen-derived molecules, products of damaged cells, toxins, or allergens lead to the release of some cell-derived mediators such as cytokines of the interleukin (IL) families, tumor necrosis factor alpha (TNF-α), prostaglan- dins (PG), nitric oxide (NO), and leukotrienes (LTs). In the first step of inflammation, high levels of lipid mediators are released, exerting either pro-inflammatory or antiinflammatory functions. Numerous agents, such as physical and chemical injury, cancer, chemotherapy, and radiation therapy, as well as bacteria and viruses, induce excessive and prolonged inflammation. While this inflammatory process plays significant roles in wound healing and microbial resistance, excessive and uncontrolled inflammation may lead to chronic diseases. Such prolonged inflammation is thought to be a common factor to many diseases, including heart, kidney, and respiratory diseases, cancer, stroke, neurological disorders (such as Alzheimer’s disease), and diabetes.
Non-steroidal antiinflammatory drugs, nowadays commonly used to treat inflammation are unfortunately associated with acute and many unwanted side-effects, like gastric ulceration, bleeding, and, in some cases, thrombosis. Scientific research points out that anti-inflammatory peptides derived from natural sources can potentially be used as promising agents against acute or chronic inflammation caused by many infectious and non-infectious diseases, what led to more comprehensive pharmacological and molecular investigations on antiinflammatory peptides and proteins over the last 20 years, including the accurate identification of the target(s) and mechanisms of their powerful antiinflammatory activities and properties. Even though some of these peptides may not be directly considered as therapeutics due to the complexity of their molecular framework, the oligomeric nature of these substances may generate ideas for the design and production of novel antiinflammatory drugs. For example,cyclic peptides have attracted an increasing interest over the past few years leading to numerous studies focusing on their potential anti-inflammatory effect in both in vivo and in vitro models of inflammation. Excitement for cyclic peptides comes from the fact that they are small enough to maintain a good cell perme-ability and yet large enough to extend the drug interface for enhanced affinity and selectivity. Thus, cyclic peptides may offer enhanced binding associations with surfaces of target proteins through their cyclic structures overcoming entropic barriers to bind proteins. The rigidity of cyclic peptides is another key factor allowing a better binding toward target molecules and receptors by considerably reducing the entropy (in term of the Gibbs free energy). For these reasons, cyclic peptides usually show a better biological activity compared to their linear counterparts. Furthermore, their cyclic structure improves their resistance to hydrolysis by exopeptidases due to the lack of both carboxyl and amino termini. There are several examples of cyclic peptides as promising anti-inflammatory agents, and several natural cyclic peptides derived from plants or marine organisms have shown significant anti-inflammatory activity and may contribute to the growth of new biopharmaceutical anti-inflammatory products in future.
Cardiac natriuretic peptides
Cardiac natriuretic peptides (sometimes also called as cardiovascular peptides) consist of three types of peptides, which are structurally very related hormones / paracrine factors and does have structurally similar molecules:
- C-type natriuretic peptides (CNP)
- atrial natriuretic peptides (ANP)
- brain natriuretic peptide (BNP)
Cardiac natriuretic peptides are secreted directly by the heart in proportion to cardiac transmural pressures and possess a wide range of effects in multiple tissues facilitating overall pressure / volume homoeostasis.
Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone consists from 28-amino acid, and with a 17-amino acid ring in the middle of his molecule. Its ring is formed by a disulfide bond between 2 cysteine residues at positions number 7 and 23. Atrial natriuretic peptides are synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart as a 126–amino acid prohormone. On secretion, this prohormone is split into an N-terminal moiety of 98 amino acids (N-ANP) and the biologically active ANP in equimolar amounts. The main function of atrial natriuretic peptides is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion. Cardiac muscle cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume. Maintenance of the ECF volume (space), and its subcompartment the vascular space, is crucial for survival. Reduction of blood volume by atrial natriuretic peptides can result in secondary effects such as reduction of extracellular fluid volume (edema), improved cardiac ejection fraction with resultant improved organ perfusion, decreased blood pressure, and increased serum potassium. These effects may be blunted or negated by various counter-regulatory mechanisms operating concurrently on each of these secondary effects. Three types of cell surface receptors have been identified on which natriuretic peptides act: guanylyl cyclase-A (GC-A, natriuretic peptide receptor-A (NPRA/ANPA) or NPR1), guanylyl cyclase-B (GC-B, natriuretic peptide receptor-B (NPRB/ANPB) or NPR2) and natriuretic peptide clearance receptor (NPRC/ANPC or NPR3). Atrial natriuretic peptides are used as biomarkers for cardiovascular diseases such as stroke, coronary artery disease, myocardial infarction and heart failure. And specific ANP precursor called mid-regional pro-atrial natriuretic peptide (MRproANP) is a highly sensitive biomarker in heart failure.
Brain natriuretic peptide (BNP) is secreted by cardiac muscle cells in the heart ventricles (cardiomyocytes), as a 108 amino-acids prohormone (proBNP). Then in circulation, glycosylated proBNP is gradually deglycosylated and further processed by the proNP convertases, corin or furin, to inactive NT-proBNP1-76 and active BNP1-32. BNP is structurally similar to ANP and shares the same guanylate cyclase receptors on endothelial cells. Brain natriuretic peptide's effect is also very similar to atrial natriuretic peptides effect. BNP acts via the same receptors as ANP, but BNP does have 10-fold lower affinity than ANP does have. The biological half-life of brain natriuretic peptide is twice as long as that half-life of atrial natriuretic peptide, and that of NT-proBNP is even longer, making these peptides better choices than atrial natriuretic peptides just for diagnostic blood testing. Brain natriuretic peptide and its N-terminal fragment (NT-BNP) are especially sensitive indicators and biomarkers of cardiac dysfunction and remodelling, and correlate strongly with severity. Given that cardiac ischaemia is also an important trigger for the release of these ventricular peptides, they may likewise play a role in the detection of coronary artery disease. Measurement of BNP/NT-BNP shows particular promise as a ‘rule out’ test for suspected cases of heart failure in both emergency care and outpatient settings, and may assist in identifying individuals with asymptomatic ventricular impairment who will benefit from therapy preventing progression to overt HF. Brain natriuretic peptides also predict subsequent haemodynamic deterioration and adverse events in cardiovascular disease, and can therefore be used to monitor those at high risk and act as a guide to optimization of treatment. The favourable biological properties of the brain natriuretic peptides have also led to their use as therapeutic agents.
C-type natriuretic peptide (CNP) is a 53 amino-acids natriuretic peptide: Cleavage of proCNP by furin yields 50 amino acid amino terminal proCNP (NT-proCNP) and CNP1-53, which is the precursor for the biologically active mature form of CNP. CNP is differentially expressed mainly in the nervous system and vasculature (e.g. endothelial cells, monocyte/macrophages) and is involved mainly in neural regulation as well as vascular control. Natriuretic peptide receptor-B (NPRB/ANPB) is just expressed mainly in endothelial cells and smooth muscle cells, and is primarily activated by CNP. Administration of CNP in vitro has been shown to exert antihypertrophic effects on cardiomyocytes as well as antiproliferative effects on vascular smooth muscle cells and primary fibroblasts. C-type natriuretic peptide has been shown to be most potent at inhibiting growth factor induced smooth muscle cell migration, and has only minimal renal actions, but it has been shown to induce vasorelaxation. Interestingly, CNP infusion to dogs has been shown to lower blood pressure more effectively than atrial natriuretic peptide without natriuretic effect.
Conclusion: Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. The close relationship between plasma concentrations of cardiac natriuretic peptides and ‘cardiac load’ has led to their use as biomarkers of cardiac health with diagnostic and prognostic applications in a variety of disorders affecting the cardiovascular system. The hemodynamic, renal, and endocrinologic effects of cardiac natriuretic peptides have been the subject of intense basic and clinical investigation for more than 15 years. Nowaday synthesized analogues of cardiac natriuretic peptides are being assessed for the treatment of acute heart failure, but still more studies need to be conducted to better understand their therapeutic effects, and also long-term effects are yet unknown.
Gastrointestinal peptide hormones
Gastrointestinal peptides (also often called as gastrointestinal hormones (GI), or gut hormones / gut peptides) are a group of hormones / predominantly polypeptides secreted by specialized enteroendocrine cells in the stomach, pancreas, and small intestine. Gastrointestinal peptide hormones control various functions of the digestive organs. Most of these peptides also play important role of neurotransmitters and neuromodulators in the central and peripheral nervous systems. Enteroendocrine cells do not form glands but are spread throughout the digestive tract, but exert their autocrine and paracrine actions that integrate gastrointestinal function. All gastrointestinal peptides are synthesized via gene transcription of DNA into messenger RNA (mRNA) and subsequently undergo translation into precursor proteins known as preprohormones. Translation occurs on ribosomes, which are complex organelles composed of many proteins and multiple large RNA molecules.
Gastrin peptide stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. The human gastrin is the product of a single gene located on chromosome 17 by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas. The final active hormone is generated from a precursor peptide preprogastrin. Preprogastrin consists from 101 amino acids including a signal peptide (21 amino acids), spacer sequence (37 amino acids), gastrin component (34 amino acids) and a 9 amino acids extension segment at the C-terminus (carboxyl end). The enzymatic processing of preprogastrin produces all of the known physiologically active forms of gastrin. Gastrin binds to cholecystokinin B receptors to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K+/H+ ATPase pumps into the apical membrane of parietal cells.
Cholecystokinin (CCK; pancreozymin) is responsible for stimulating the digestion of fat and proteins, and is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Cholecystokinin's presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as hunger suppressant.
Peptide Secretin iregulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. Secretin is produced in the S cells of the duodenum (which are located in the intestinal glands), and helps regulate the pH of the duodenum by inhibiting the secretion of gastric acid from the parietal cells of the stomach and stimulating the production of bicarbonate from the ductal cells of the pancreas. Secretin peptide also stimulates bile production by the liver; the bile emulsifies dietary fats in the duodenum so that pancreatic lipase can act upon them. In year 2007 was found, secretin play also role in osmoregulation by acting on the hypothalamus, pituitary gland, and kidney. Secretin peptide is first synthesized as a 120 amino acid precursor protein prosecretin. It contains an N-terminal signal peptide, spacer, secretin itself (AA residues 28–54), and a 72-amino acid C-terminal peptide. The mature secretin peptide is a linear peptide hormone, which is composed of 27 amino acids and has a molecular weight of 3055. Its A helix is formed in the amino acids between positions 5 and 13; and its amino acids sequences does have some similarities to that of glucagon, vasoactive intestinal peptide (VIP), and gastric inhibitory peptide (GIP): Fourteen of 27 amino acids of secretin reside in the same positions as in glucagon, 7 the same as in vasoactive intestinal peptide, and 10 the same as in gastric inhibitory peptide. Secretin also has an amidated carboxyl-terminal amino acid which is valine.
Peptide hormone Somatostatin (growth hormone-inhibiting hormone; GHIH) is a cyclic peptide that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion. It has two biologically active forms produced by the alternative cleavage of a single preproprotein: While one consisting of 14 amino acids, the other consisting of 28 amino acids. Somatostatin-14 is identical to the carboxyl terminal 14 amino acids of somatostatin-28. Both forms - somatostatin-14 and somatostatin-28 are the products of post-translational processing of preprohormone. Somatostatin is produced by both, digestive system and also in brain. In digestive system Somatostatin is secreted by delta cells at several locations in the digestive system, namely the pyloric antrum, the duodenum and the pancreatic islets. Somatostatin released in the pyloric antrum travels via the portal venous system to the heart, then enters the systemic circulation to reach the locations where it will exert its inhibitory effects. In addition, somatostatin release from delta cells can act in a paracrine manner. In the stomach, somatostatin acts directly on the acid-producing parietal cells via a G-protein coupled receptor (which inhibits adenylate cyclase, thus effectively antagonising the stimulatory effect of histamine) to reduce acid secretion. Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones, including gastrin, secretin and histamine which effectively slows down the digestive process.
In brain, somatostatin is produced by neuroendocrine neurons of the ventromedial nucleus of the hypothalamus. These neurons project to the median eminence, where somatostatin is released from neurosecretory nerve endings into the hypothalamohypophysial system through neuron axons. Somatostatin is then carried to the anterior pituitary gland, where it inhibits the secretion of growth hormone from somatotrope cells. The somatostatin neurons in the periventricular nucleus mediate negative feedback effects of growth hormone on its own release; the somatostatin neurons respond to high circulating concentrations of growth hormone and somatomedins by increasing the release of somatostatin, so reducing the rate of secretion of growth hormone. Somatostatin is also secreted by several other populations that project centrally, i.e., to other areas of the brain, and somatostatin receptors are expressed at many different sites in the brain. In particular, populations of somatostatin neurons occur in the arcuate nucleus, the hippocampus, and the brainstem nucleus of the solitary tract.
Effects of somatostatin in the anterior pituitary gland:
- Inhibits the release of growth hormone (thus opposing the effects of growth hormone–releasing hormone)
- Inhibits the release of thyroid-stimulating hormone (TSH)
- Inhibits adenylyl cyclase in parietal cells
- Inhibits the release of prolactin (PRL)
Effects of somatostatin in the gastrointestinal system:
- Suppresses the release of gastrointestinal hormones
- Decreases the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine
- Suppresses the release of pancreatic hormones
- Somatostatin release is triggered by the beta cell peptide urocortin3 (Ucn3) to inhibit insulin release
- Inhibits the release of glucagon
- Suppresses the exocrine secretory action of the pancreas
Ghrelin: Important 28-amino-acid peptide and natural ligand of the growth hormone secretagogue receptors (GHS-R) Ghrelin (Lenomorelin) is produced mainly by ghrelinergic cells in the gastrointestinal tract and it acts as a neuropeptide in the central nervous system, regulates appetite, and also plays a important role in regulating energy homeostasis. When the stomach is empty, then ghrelin is secreted, and when the stomach is full, then secretion of ghrelin stops. Ghrelin acts on hypothalamic brain cells both to increase hunger, and to increase gastric acid secretion and gastrointestinal motility to prepare the body for food intake. Ghrelin also haves important function in regulating reward cognition in dopamine neurons that link the ventral tegmental area to the nucleus accumbens (a site that plays a role in processing sexual desire, reward, and reinforcement, and in developing addictions) through its colocalized receptors and interaction with dopamine and acetylcholine.
The GHRL gene produces mRNA which has four exons; and gradually 5 peptide products are produced in total:
- The first peptide that is produced is 117-amino acid preproghrelin
- Then preproghrelin is cleaved to produce proghrelin
- Proghrelin is cleaved to produce a 28-amino acid ghrelin (unacylated ghrelin)..
- And C-ghrelin (acylated ghrelin)
- Fifth peptide Obestatin is presumed to be cleaved from C-ghrelin
Ghrelin producing cells occur in multiple organs in the human body:
- mainly in the stomach and duodenum, but also:
- in jejunum
- in lungs
- in pancreatic islets
- in gonads
- in adrenal cortex
- in placenta
- in kidney
- and recently has been shown ghrelin is also produced locally in the brain
Ghrelin binds to GHS-R-1A receptor (growth hormone secretagogue receptor 1A). Also a second variant of growth hormone secretagogue receptor exists in a truncated form - growth hormone secretagogue receptor 1B (GHS-R-1B). Growth hormone secretagogue receptor 1A is found within hypothalamic (ventromedial nucleus and arcuate nucleus), brainstem and forebrain areas of relevance for feeding control, but is also presents in large amount in the pituitary, on the vagus nerve, in the gastrointestinal tract. Outside the central nervous system, growth hormone secretagogue receptors are also found in the liver, in skeletal muscle, and even in the heart and reproductive organs.
Known locations and organs where ghrelin acts in the human body:
- Pancreas: Ghrelin inhibits glucose-stimulated insulin secretion from beta cells in the pancreatic islets.
- Glucose metabolism: The entire ghrelin system (dAG, AG, GHS-R and GOAT) has a gluco-regulatory action.
- Nervous system:
- Learning and memory: The hippocampus (small region of the brain that forms part of the limbic system and is primarily associated with memory and spatial navigation) plays a significant role in neurotrophy - the cognitive adaptation to changing environments and the process of learning and it is a potent stimulator of Growth hormone (GH). Animal models indicate that ghrelin may enter the hippocampus from the bloodstream, altering nerve-cell connections, and so altering learning and memory. It is suggested that learning may be best during the day and when the stomach is empty, since ghrelin levels are higher at these times.
- Depression: Ghrelin has been shown to hav antidepressant-like attributes, acts as a short-term natural adaptation against depression.
- Sleep duration: Short sleep duration is associated with high levels of ghrelin and obesity. An inverse relationship between the hours of sleep and blood plasma concentrations of ghrelin exists; as the hours of sleep increase, ghrelin levels trend lower and obesity is less likely.
- Substantia nigra function: Ghrelin, through its receptor increases the concentration of dopamine in the substantia nigra.
- Stress-induced fear: Stress-related increases in ghrelin circulation were shown to be necessary and sufficient for stress to increase fear learning. Ghrelin was found to be upregulated by stress even in the absence of adrenal hormones. Blocking the ghrelin receptor during stress abolished stress-related enhancement of fear memory without blunting other markers of stress. These results suggest that ghrelin is a novel branch of the stress response. Human studies are needed to translate the use of anti-ghrelin treatments to prevent stress-induced psychiatric disorders.
- Reproductive system: Ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion, what may cause decreased fertility.
- Fetus and neonate: Ghrelin is produced early by the fetal lung and promotes lung growth. Cord blood levels of active and total ghrelin show a correlation between ghrelin levels and birth weight.
Motilin is a 22-amino acid polypeptide with molecular weight of 2698 Daltons, released by endocrine Mo cells or M cells, that are numerous in crypts of the small intestine, especially in the duodenum and jejunum. In humans, motilin is encoded by the MLN gene. Motilin is released into the general circulation in humans at about approx. 100-min intervals during the inter-digestive state and is the most important factor in controlling the inter-digestive migrating contractions. It also stimulates endogenous release of the endocrine pancreas.
The Pancreatic polypeptide family includes 3 peptides, all three does have the same length amino-acids string of 36 amino acids:
- Pancreatic polypeptide (PP)
- Peptide YY (PYY, YY)
- Neuropeptide Y (NPY)
Pancreatic polypeptide is expressed in endocrine cells of the gut and pancreas, and it has peripheral effects on the gastrointestinal tract and could reduce food intake. Pancreatic polypeptide therefore appears to have the potential to act as a long-term appetite suppressor and thus may be a suitable target for antiobesity drug design. Peptide YY is located in enteroendocrine cells of the ileum and colon where it is co-stored with glucagon-like peptide-1 (GLP-1) and nerves of the enteric nervous system. Howewer, the main form of peptide YY stored in the gut and found in the circulation is the N-terminally truncated peptide YY3–36. The different forms of peptide YY have different receptor affinities, reflecting their different biological effects. Although full-length peptide YY binds with similar affinity to all of the members of the Y receptor family, peptide YY3–36 has high affinity only for the Y2 and a lesser affinity for Y1 and Y5 receptors. Peptide YY3–36 reduces food intake, is important in energy and glucose homeostasis. Peptide YY3–36 may have utility as an obesity therapy. Circulating peptide YY levels are lower in the obese, suggesting that low peptide YY levels may have a causative role in the development of obesity.
Neuropeptide Y is located in the central and peripheral nervous system, it is released alongside other neurotransmitters such as GABA and glutamate; and is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. Neuropeptide Y is produced mainly by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue. In the brain, it is produced in various locations including the hypothalamus, and is thought to have several functions, including: increasing food intake and storage of energy as fat, reducing anxiety and stress, reducing pain perception, affecting the circadian rhythm, reducing voluntary alcohol intake, lowering blood pressure, and controlling epileptic seizures. Neuropeptide Y exerts most of its effects through G-protein coupled receptor proteins, mainly Y1, Y2, Y4, and Y6. The receptor protein that neuropeptide Y operates on is a G protein-coupled receptor in the rhodopsin like 7-transmembrane GPCR family. Subtypes of the neuropeptide Y receptor Y1 and Y5 have known roles in the stimulation of feeding while Y2 and Y4 seem to have roles in appetite inhibition. Some of these receptors are among the most highly conserved neuropeptide receptors. High concentrations of neuropeptide Y synthesis and action have been found in the hypothalamus and hippocampus, specifically in the arcuate nucleus and dentate gyrus. The arcuate nucleus has been found to have one of the highest concentrations of neuropeptide Y. This allows this peptide to regulate neuroendocrine release of various hypothalamic hormones such as luteinizing hormone. Neuropeptide Y1 receptors have been found in highest density in the dentate gyrus along with a variety of other brain areas. Neuropeptide Y also cast an important role in cell neurogenesis in various parts of the brain. Two particular brains areas of where neuropeptide Y affects neurogenesis are the sub-ventricular zone and the dentate gyrus of the hippocampus. These areas are where cell growth and proliferation occur into adulthood. This wide distribution of these peptides suggests that their regulate many different and important physiological processes in the body.
Glucagon-like peptide-1 (GLP-1) is 31 amino acid peptide hormone released from the L-cells of the gastrointestinal tract and certain neurons within the nucleus of the solitary tract in the brainstem, postprandially in proportion to the calories ingested. The initial product glucagon-like peptide-1 (1–37) is susceptible to amidation and proteolytic cleavage which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active glucagon-like peptide-1 composes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region. Glucagon-like peptide-1 haves insulinotropic effects - the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin; and is also associated with numerous other regulatory and protective effects. The main effect of glucagon-like peptide-1 is its ability to promote insulin secretion in a glucose-dependent manner. As glucagon-like peptide-1 binds to GLP-1 receptors expressed on the pancreatic β cells, the receptors couples to G-protein subunits and activates adenylate cyclase that increases the production of cAMP from ATP. Subsequently, activation of secondary pathways, including PKA and Epac2, alters the ion channel activity causing elevated levels of cytosolic Ca2+ that enhances exocytosis of insulin-containing granules. During the process, influx of glucose ensures sufficient ATP to sustain the stimulatory effect. Additionally, glucagon-like peptide-1 ensures the β cell insulin stores are replenished to prevent exhaustion during secretion by promoting insulin gene transcription, mRNA stability and biosynthesis. Glucagon-like peptide-1 evidently also increases β cell mass by promoting proliferation and neogenesis while inhibiting apoptosis. As both type 1 and 2 diabetes are associated with reduction of functional β cells, this effect is highly interesting regarding diabetes treatment. In the brain, glucagon-like peptide-1 receptor activation has been linked with neurotrophic effects including neurogenesis and neuroprotective effects including reduced necrotic and apoptotic signalling and cell death. In the stomach, glucagon-like peptide-1 inhibits gastric emptying, acid secretion and motility collectively decreasing appetite - diminish ghrelin-triggered effects on food intake and gastric emptying and lead to a reduction of ghrelin release. Glucagon-like peptide-1 has also shown signs of carrying out protective and regulatory effects in numerous other tissues, including heart, tongue, adipose, muscles, bones, kidneys, liver and lungs.
Oxyntomodulin is 37-amino acid peptide hormone found in the colon, produced by the oxyntic cells of the oxyntic mucosa, and that binds to the glucagon-like peptide-1 receptor. Oxyntomodulin is inhibitor of gastric acid secretion, and also reduces food intake / decreases appetite. Clinical studies proven that oxyntomodulin administration significantly reduced energy intake from meal, but also increased activity-related energy expenditure by more than 25%. This suggests, that oxyntomodulin may be potential and high effective treatment of obesity in the future.
Gastric inhibitory polypeptide (GIP; glucose-dependent insulinotropic peptide) is inhibitor of the secretin family gastrointestinal peptide hormones, its main role is to stimulate insulin secretion. Gastric inhibitory polypeptide is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide; it is produced by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. Like other endocrine hormones, gastric inhibitory polypeptide is also transported by blood, and its receptors are seven-transmembrane proteins found on beta-cells in the pancreas.
Vasoactive intestinal peptide (VIP) is hormone that is vasoactive in the intestine. It have amino acid sequence consits of 28 amino acid residues; and belongs to a glucagon / secretin superfamily of gastrointestinal peptide hormones, which are ligands of class II G protein–coupled receptors. Vasoactive intestinal peptide is produced in many tissues of vertebrates including the gut, pancreas, and suprachiasmatic nuclei of the hypothalamus in the brain. This peptide stimulates contractility in the heart, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gall bladder.
|Peptide hormone||Major tissue locations in the gut||Principal known actions|
|Bombesin||Throughout the gut and pancreas||Stimulates release of cholecystokinin (CCK) and gastrin|
|Calcitonin gene-related peptide||Enteric nerves||Unclear|
|Chromogranin A||Neuroendocrine cells||Secretory protein|
|Enkephalins||Stomach, duodenum||Opiate-like actions|
|Enteroglucagon||Small intestine, pancreas||Inhibits insulin secretion|
|Ghrelin||Stomach||Stimulates appetite, increases gastric emptying|
|Glucagon-like peptide 1||Pancreas, ileum||Increases insulin secretion|
|Glucagon-like peptide 2||Ileum, colon||Enterocyte-specific growth hormone|
|IGF-1||Throughout the gut||Cell proliferation and differentiation|
|Growth hormone-releasing factor (GHRF)||Small intestine||Unclear|
|Motilin||Throughout the gut||Increases gastric emptying and small bowel motility|
|Neuropeptide Y||Enteric nerves||Regulation of intestinal blood flow|
|Neurotensin||Ileum||Affects gut motility; increases jejunal and ileal fluid secretion|
|Pancreatic polypeptide||Pancreas||Inhibits pancreatic and bilary secretion|
|Peptide YY||Colon||Inhibits food intake|
|Somatostatin||Stomach, pancreas||Inhibits secretion and action of many hormones|
|Substance P||Enteric nerves||Unclear|
|Trefoil peptides||Stomach, intestine||Mucosal protection and repair|
Anti-aging effect of peptides
Peptides and anti-aging: Many clinical trials and biological research results have indicated that several peptides (mainly peptides associated with maintaining a healthy level of natural human growth hormone, often called as an anti-aging peptides) may have potential anti-aging capabilities and/or remedial effects for body and various internal organs. These peptides appear to be very promising substances that could help in the future to effectively slow down aging and significantly prolong human life. Therefore, they are object of great interest not only for scientists, medical doctors and specialists in the field of biology, but also for many other people.
However, this is an area that is still little and insufficiently researched and requires much more scientific research, knowledge and exploration. The dream of every human being is not to age and live for a long time, and perhaps it is the peptides that may be those imaginary miraculous substances that could at least partially help to fulfill this dream and significantly slow down aging and prolong human life.
Skin peptides and Cosmetic peptides
Aging: Is a natural process that manifests itself over time in all living ogranisms including humans, and follows different trajectories in different organs, tissues and cells in whole body. Most striking and simplest (with the naked eye) visible signs of aging and time passing are usualy manifest on the skin. At the same time, skin health (especially face skin health) is often considered to be one of the main factors suggesting overall human health and condition of the body. Aging of skin and skin changes over time is a complex biological process influenced by combination of several endogenous (intrinsic) factors such as genetics, cellular metabolism, hormone and metabolic processes; and exogenous (extrinsic) factors, such as chronic light exposure, pollution, ionizing radiation, chemicals and toxins (harmful factors that can damage the skin and cause it to age rapidly).
All these mentioned factors lead together to cumulative structural, physiological and progressive alterations in each skin layer and also changes in skin appearance. But aging of the entire face is associated with several other factor (not only with skin aging), such as: work of face muscles, loss of volume, diminishing and redistribution of superficial and deep fat and loss of bony skeleton; this all together lead to the face sagging, changes in shape and contour.
Skin anti-aging research: Principally, 3 primary structural components of the dermis have been most studied by majority of anti-aging research and efforts for aesthetic anti-aging strategies pertaining to the skin:
Collagen: Endogenous protein collagen is the main structural protein in the extracellular space in the various connective tissues in the body. Collagen is also a major component of our skin, it is responsible for firm, healthy and young looking skin. But as we age, our body gradually produces less collagen (and elastin), as a result, the skin becomes dry and less hydrated, begins to lose its powers of regeneration and wrinkles are formed. Collagen is often used in skin care cosmetics as the active ingredient of anti-wrinkle creams, or directly as dermal fillers in anti-wrinkle injection / injectable skin rejuvenation therapies to treat wrinkles and skin aging. Additionally, collagen supplements also can stimulate production of other dermal proteins that support rejuvenate of skin (such as elastin or fibrillin).
Elastin: Is a highly elastic endogenous protein in connective tissue and allows many tissues in the body to resume their shape after stretching or contracting, and helps skin to return to its original position when it is poked, deformed or pinched. In the body, elastin is usually associated with other proteins in connective tissues. Elastic fiber in the body is a mixture of amorphous elastin and fibrous fibrillin. An interesting property of elastin is its biological half-life: It is a protein with a very long lifetime, with a half-life of over 78 years in humans.
Glycosaminoglycans: Glycosaminoglycans (GAGs; mucopolysaccharides) are long linear unbranched polysaccharides consisting of repeating disaccharide (double sugar) units. The repeating unit (except for keratan) consists of an amino sugar (N-acetylglucosamine or N-acetylgalactosamine) along with a uronic sugar (glucuronic acid or iduronic acid) or galactose. Glycosaminoglycans are highly polar and attract water; they are therefore useful to the body as a lubricant or as a shock absorber.
Based on core disaccharide structures, GAGs are classified into four groups:
- Heparin/heparan sulfate (HSGAGs)
- chondroitin sulfate/dermatan sulfate (CSGAGs)
- Keratan sulfate types
- Hyaluronic acid (HA)
Hyaluronic acid (HA): Hyaluronic acid is a major component of synovial tissues and fluid, as well as other soft tissues, and endows their environments with remarkable rheological properties. It is also often used as a component of anti-aging agents and cosmetics. Hyaluronic acid exhibits no species or tissue specificity. As a physical background material, hyaluronic acid functions in space filling, lubrication, shock absorption, and protein exclusion. In addition, hyaluronic acid has been implicated as a regulator of cell proliferation and locomotion.
Skin anti-aging peptides can be helpful and highly effective in significantly slowing down skin aging or in skin recovery, rejuvenation and regeneration processes, and are widely used as active agents of anti-aging skin care and key elements of skin anti-aging strategies. They have strong ability to stimulate and boost collagen production and (re)activate dermal metabolism, or other useful properties and remedial effects for for skin, therefore they are a frequent component / ingredients of anti-wrinkle creams, cosmetic eye-bag, serums, fillers etc. Polypeptides or oligopeptides can sldo imitate a peptide sequence of molecules such as collagen or elastin.
Main types of peptides used in skin care:
- Neurotransmitter inhibitor skin peptides
- Signal skin peptides
- Carrier skin peptides
- Enzyme inhibitor skin peptides
Neurotransmitter inhibitor skin peptides: This kind of skin peptides provide relaxing effect on your facial muscles (act against the contraction of muscles), minimize movement and the formation of wrinkles (similar effect as Botox does). But it is important to note that these peptides can only prevent wrinkles formed due to facial expressions. Neurotransmitter inhibitor skin peptides class includes peptides such as Acetyl hexapeptide-3 (Argireline), Pentapeptide-18 (Leuphasyl), Pentapeptide-3 (Vialox), Syn-Ake (Synake, Tripeptide-3, Dipeptide diaminobutyroyl benzylamide diacetate) or Acetyl octapeptide-1 (SNAP-8).
Signal skin peptides: This kind of skin peptides boost and stimulate collagen, hyaluronic acid, fibronectin and laminin 5 natural production. Also they may have ability protect against UV damage or inflammation, enhance skin regeneration, improve healing and skin elasticity.
List of popular signal skin peptides often used in anti-aging skin care & anti-wrinkle cosmetics products:
- Palmitoyl Tetrapeptide-7, Palmitoyl Tripeptide-1 and Palmitoyl Oligopeptide: Signal skin peptides Palmitoyl Tetrapeptide-7 and Palmitoyl Tripeptide-1 are key substances in Matrixyl-3000 (trademarked peptide composition developed by Sederma Inc), and often are used with Palmitoyl Oligopeptide. This combination of peptides may strong ability to significantly boost natural collagen production in the skin.
- Palmitoyl Tripeptide-38: Stimulate production of dermal and epidermal important components: collagen I, III, and IV, fibronectin, hyaluronic acid and laminin 5.
- Bio-mimetic peptide Tripeptide KMK: Also stimulates production of major structural components of the dermal matrix: collagen I, III, IV, fibronectin, hyaluronic acid and laminin.
- Tripeptide-10 citrulline: One of several molecules that controll regulation of collagen fibres is decorin. With aging, decorin activity declines. Tripeptide-10 citrulline mimic decorin, and with this way stimulate collagen production.
- Palmitoyl Pentapeptide-4 (called also as Matrixyl and Palmitoyl Pentapeptide-3): Activate certain genes involved in the process of extracellular matrix renewal and cell proliferation, and by this way provides an anti-wrinkle effect.
- Tripeptide Palmitoyl Tripeptide-5: Is highly bioactive, deeply skin penetrating peptide that does have ability to protect and boost collagen production. Palmitoyl Tripeptide-5 activate tissue growth factor (TGF-beta); that stimulate collagen synthesis in the skin.
- Trifluoroacetyl-Tripeptide-2: This peptide inhibite the production of progerin (cell-aging accelerator protein), increase proteoglycan production, and improve skin elasticity and firmness.
Carrier skin peptides: This kind of skin peptides, as the name itself suggests, does have ability to carries trace elements (for example such as copper or manganese) to the skin, and by this way they may help to better skin elasticity, increase wounds healing, or boost collagen natural production. To this group belong for example copper peptides or X-50 Myocept powder.
Enzyme inhibitor skin peptides: These skin peptides does have ability to inhibite enzymes that are responsive for the breakdown of collagen production, and prevent matrix metalloproteinases to work properly (matrix metalloproteinases are group of enzymes responsible for collagen destruction / degradation). To the group of enzyme inhibitor skin peptides belongs for xample Trylagen, soybean peptides or silk fibroin peptides, but also Trifluoroacetyl-Tripeptide-2.
Dermal fillers and skin biorejuvenation: One of the most effective methods of skin biorejuvenation is direct application of dermal fillers into the skin by cosmetic microinjections in the superficial dermis. Target of this type of skin anti-aging therapy is to increase the biosynthetic capacity of fibroblasts, inducing the reconstruction of an optimal physiologic environment, the enhancement of cell activity, hydration, and the synthesis of collagen, elastin and hyalorunic acid.
Injection of hyaluronic acid is thought to promote skin rejuvenation by increasing both hydration and fibroblast activation. Hyaluronic acid injected into the skin can stimulate fibroblasts to express Col-1, MMP-1 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) as well as is participating in wound healing, modulation of inflammatory cells, interaction with proteoglycans of the extracellular matrix, and scavenging of free radicals. All these features of hyaluronic acid have made it to be useful as an ideal structural compound and have raised injections of hyaluronic acid products to the most acceptable and scientifically investigated gold standard procedures for skin rejuvenation. The duration of effect for hyaluronic acid fillers ranges from 3 to 12 months. The long-lasting dermal fillers maintain the position 1–2 years or even more. One of long-lasting synthetic semi-permanent dermal fillers is calcium hydroxyl apatite based filler (CaHA) suspended in an aqueous carboxymethylcelluose gel carrier. The CaHA particles act as a scaffold for new tissue formation and stimulate collagen formation around the microspheres leading to a thickening of the dermis over time. The spherical CaHA particles are gradually phagocytosed, degraded as calcium and phosphate and eliminated via the renal system. CaHA is biocompatible with an identical composition to bones with a low potential for antigenicity, foreign body reaction, and minimal inflammatory response. No osteoblast activity has been observed in soft tissue.
Antioxidants, vitamins, polyphenols and flavonoids: They are another often used substances with skin anti-aging properties that have ability to reduce collagen degradation by reducing the concentration of free radicals in the tissues. Vitamins C, B3, and E are the most important antioxidants because of their ability to penetrate the skin through their small molecular weight. The water-soluble, heat-labile local L-ascorbic acid (vitamin C) in concentrations between 5 and 15% was proven to have a skin anti-aging effect by inducing the production of Col-1, and Col-3, as well as enzymes important for the production of collagen, and inhibitors of matrixmetalloproteinase (MMP) 1 (collagenase 1). Clinical studies have proven that the antioxidative protection is higher with the combination of vitamins C and E than with the vitamin C or E alone. Niacinamide (vitamin B3) regulates cell metabolism and regeneration, and it is used in 5% concentration as an anti-aging agent. In some studies, improvement of skin elasticity, erythema and pigmentations after 3 mo of topical treatment has been observed. Vitamin E (α-tocopherol) used as a component of skin products has anti-inflammatory and antiproliferative effects in concentrations between 2 and 20%. It acts by smoothing the skin and increasing the ability of the stratum corneum to maintain its humidity, to accelerate the epithelialization, and contribute to photoprotection of the skin. The effects are not as strong as with vitamins C and B3.
Cell regulators, such as vitamin A derivatives, polypetides and botanicals, act directly on the collagen metabolism and stimulate the production of collagen and elastic fibers. Vitamin A (retinol) and its derivates (retinaldehyde and tretinoin) are also a group of agents with antioxidant effects. They can induce the biosynthesis of collagen and reduce the expression of MMP 1 (collagenase 1). Retinol is, at the moment, the substance that is most often used as an anti-aging compound and, compared with tretinoin, causes less skin irritation. It has been shown that retinol has positive effects not only on extrinsic but also on intrinsic skin aging and has a strong positive effect on collagen metabolism. Tretinoin, a nonaromatic retinoid of the first generation, is approved for application as an anti-aging treatment in a concentration of 0.05% in the United States. It has been shown to be able to reduce the signs of UV-induced early skin aging, such as wrinkles, loss of skin elasticity and pigmentation.
Ribosomal peptides are produced in ribosomes - complex macromolecular mechanisms that are found in all living cells and whose function is the synthesis of biological proteins and ribosomal peptides (protein biosynthesis). The sequence of the amino acids in protein or peptide is encoded in the DNA (Deoxyribonucleic acid), and this genetic information (about the amino acid sequence) is transferred from the DNA to the ribosomes by messenger RNA (mRNA). mRNA is a large family of RNA (Ribonucleic acid) molecules, that convey genetic information from DNA to the ribosomes. Based on this transmitted important genetic information, ribosomes can join amino acids together exactly in correct & right order (specified by mRNA molecules). The whole process proceeds as follows: The sequence of DNA, which encodes the sequence of the amino acids in a protein or in a peptide, is copied into a messenger RNA chain. (It may be copied many times into RNA chains.) Ribosomes can bind to a messenger RNA chain and use its sequence for determining the correct sequence of amino acids for generating a given protein or peptide: Amino acids are selected, collected, and carried to the ribosome by transfer RNA (tRNA) molecules, which enter one part of the ribosome and bind to the messenger RNA chain. (Using the mRNA as a template, the ribosome traverses each codon (3 nucleotides) of the mRNA, pairing it with the appropriate amino acid provided by an aminoacyl-tRNA.) It is during this binding that the correct translation of nucleic acid sequence to amino acid sequence occurs. Very important is, for each coding triplet in the messenger RNA there is a distinct transfer RNA that matches and which carries the correct amino acid for that coding triplet. The attached amino acids are then linked together by another part of the ribosome. The process in which ribosomes synthesize proteins or peptides after the process of transcription of DNA to RNA in the cell's nucleus, is in biology called translation (of mRNAs); and the entire process is called gene expression. Some ribosomal peptides are subject to proteolysis, when mature peptide is form by removing some fragments from the source polypeptide or protein. Typically, they function and act as hormones and signaling molecules in higher organisms. Most of ribosomal peptides are linear, and undergo further post-translational modifications (hydroxylation, phosphorylation, glycosylation, sulfonation or disulfide-formation).
Non-ribosomal peptides (NRP) are synthesized by one or more specialized enzymes, called nonribosomal peptide-synthetase (NRPS), and not by ribosomes. Nonribosomal peptide-synthetases, unlike ribosomes, are independent of messenger RNA. As a rule, each NRPS can synthesize only one type of peptide. The biosynthesis of nonribosomal peptides shares characteristics with the polyketide and fatty acid biosynthesis. Due to these structural and mechanistic similarities, some nonribosomal peptide synthetases contain polyketide synthase modules for the insertion of acetate or propionate-derived subunits into the peptide chain. Non-ribosomal peptides are a class of peptide secondary metabolites, usually produced by microorganisms (like bacteria and fungi). They are also found in some higher organisms, however, it is believed that they are made up of bacteria inside these organisms. Non-ribosomal peptides often contain cyclic and / or branched structures, can contain non-proteinogenic amino acids including D-amino acids, carry modifications like N-methyl and N-formyl groups, or can be glycosylated, acylated, halogenated, or hydroxylated. Non-ribosomal peptides are a very diverse family of natural compunds, which have very broad range of biological activities and pharmacological properties, they are often toxins, siderophores, or pigments.
Popular peptides quick review
Melanotan 2 is synthetic analogue of endogenous peptide of melanocortin family, α-melanocyte-stimulating hormone (α-MSH), that has been studied in many scientific and clinical studies. The most interesting properties of Melanotan 2 for scientists, include its strong ability to significantly stimulate pigment production in skin (by activation of the MC1 receptor), strong ability to increase libido, potency and sexual activity (by activation of the MC4 receptor) and suppressing hunger (the ability treat of obesity). Peptide melanotan 2 is also intensive investigated as a possible effective skin protection against the harmful effects of UV rays and skin cancer.
GHRP-6 is synthetic analogue of Met-Enkephalin, contains unnatural (synthetic) D-amino acids. This peptide belongs to growth hormone secretagogues group and has strong gh-releasing effect; GHRP-6 stimulates the production of natural, endogenous growth hormone in the body, both in humans and animals. GHRP-6 act as synthetic ghrelin mimetic, and is binding on the same ghrelin receptors as ghrelin. With this way GHRP-6 triggers and stimulates production of endogenous gh in somatotropic cells.
IGF-1 protein (Insulin-like growth factor 1) is hormone with similar molecular structure like further key peptide hormone insulin. IGF-1 is formed by 70 amino acids in a single chain with three intramolecular disulfide bridges. In childhood is IGF-1 important for growth and development, in adults is IGF-I responsible for overall anabolic processes in the body (protein and amino acids synthesis), cell growth, proliferation, regeneration. IGF-1 peptide can regulate cellular DNA synthesis; and in the brain IGF-1 acts as a neurotrophic factor that, like BDNF, plays important role in cognition, neurogenesis, and neuronal survival.
Follistatin-344 activin-binding protein is a single-chain gonadal autocrine monomeric glycoprotein / peptide, expressed in nearly all tissues of higher animals and humans. Follistatin peptide bioneutralize members of transforming growth factor beta superfamily (TGF-β), include GDF-8 (Growth Differentiation factor 8/ myostatin), and with a particular effect on paracrine hormone activin. Scientists know various different isoforms of Follistatin peptides, as Follistatin-344 (FST344), Follistatin-317 (FST317), Follistatin-315 (FST315), Follistatin-300 (FST300) or Follistatin-288 (FST288).
Growth hormone (GH) is 191-amino acid single-chain poly-peptide encoded by the GH1 gene. The most important function of HGH is stimulation through the JAK-STAT signaling pathway of IGF-1, and many functions / effects that are generally attributed or associated with HGH, in fact are caused right by IGF-1. Most important known related effects and functions associated and related with growth hormone include growth (in body height) during childhood, increase of protein synthesis, lipolysis promotion and utilization of fat by stimulating triglyceride breakdown and oxidation in adipocytes, support of whole body regeneration, wound healing and tissue rebuild, increase of calcium retention - increase the mineralization of bone, and gh also may reduce risk of heart and cardio-vascular diseases.
HGH fragment peptide is short synthetic part sequences of growth hormone. HGH fragment is a modified form of amino acids 176-191 at the C-terminal region of the growth hormone, which works by mimicking the way natural gh regulates fat metabolism, but without the affect on insuline levels, because just part 176-191 of aminoacid seqeunce of growth hormone represents its fat burning power. Clinical test confirms, in both humans also animals, this fragment peptide leads to lipolysis (breakdown of fat) and inhibits lipogenesis. Scientific studies and clinical trials have shown that HGH Fragment released fat specifically from obese fat cells, but not from lean cells. Research also suggested that HGH fragment peptide simultaneously strongly reduce new fat accumulation in all fat cells, and improve whole burning of fat.
CJC-1295 is a 30-amino acid peptide which is synthetic analogue and modified form of somatocrinin. Peptide CJC-1295 increase and stimulate plasma growth hormone and IGF-1 levels in both animals and humans, without affecting the pulsatility of growth hormone secretion. CJC 1295 peptide is marked by its capacity to bioconjugate with the globular protein serum albumin and has the capacity to pair up two biomolecules together in a chemical bond. This rapidly extends its biologically half-life.
MGF (IGF-1Ec) is splicing variant of peptide IGF-1, that has been found in many tissues, and is produced directly in target tissues as paracrine/autocrine hormone. IGF-1Ec peptide is dependent on the IGF-1 Receptor (IGF-1R) and directly stimulates the IGF-1R. Mechanical overload or damage significantly leads in muscle tissues to the synthesis of Igf1 mRNA. IGF-I are upregulated in hypertrophic muscles and stimulate satellite cells. IGF-1 leads to increased differentiation and hypertrophy.
DES(1-3)IGF-1 is truncated analogue of peptide IGF-1, but difference in structure between IGF-1 and DES(1-3)IGF-1 is that DES(1-3)IGF-1 lacks the first three amino acids (tripeptide Gly-Pro-Glu) at the N-terminus of IGF-1 (while IGF-1 is formed by 70 amino acids, DES(1-3)IGF-1 by 67 amino acids). Peptide DES(1-3)IGF-1 binds with high-affinity to IGF-1 receptor, what results to activation of an array of genes that mediate cellular function.
ACE-031 is scientifically engineered decoy receptor. ACE-031 is a soluble and synthetic form of transmembrane protein receptor called ACVR2B (activin receptor type IIB; also marked as ActRIIB). Both, ACVR2B and ACE-031 are receptors with high affinity to bind myostatin (GDF-8) and related ligands from TGF-β (transforming growth factor beta) superfamily, that negative affects muscle growth and rebuild. ACE-031 may ability prevent myostatin to bind ACVR2B in muscle-fiber membranes, and prevents delivering myostatin's muscle growth-limiting signal to the muscle cells. Researchers hope, ACE-031 can help maintain and improve muscles in patients with symptom of many neuromuscular diseases including muscular dystrophy, and can be useful as possible treatment in future to help treat muscle weakness and deterioration.
Pentapeptide Ipamorelin is a modern, highly selective and potent synthetic met-enkephalin analog that include unnatural D-amino acids, from subgroup of Ghrelin receptors. Similar as GHRP-6 and other Ghrelin receptors agonists, ipamorelin also acts as synthetic Ghrelin mimetic and haves significantly growth hormone releasing activity and effect. Peptide ipamorelin does not affect prolactin, adrenocorticotropic hormone (ACTH) or cortisol, because ipamorelin is highly selective for inducing the secretion of growth hormone only. For many advantages (particularly for its selectivity) over other ghrelin mimetics is Ipamorelin very interesting candidate for further scientific research and clinical development.
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Today, scientists know and record complete amino acid sequences of more than 100,000 peptides and proteins, wherein each such peptide or protein has its unique and precisely defined amino acid sequence. There are many peptides discovered and many kinds of peptides are known. Peptides can be sorted, classified or categorized according to numerous factors or their properties, such as chemical structure and properties, number of amino acids, functions and operation, occurrence, place of action, source, origin etc. There are many peptide types and kinds also in our peptide sale. Unique chemical and physical properties of peptides directly depend on composition and bindings of their amino acid.
The peptides may be produced naturally (they are naturally synthesized in all living organisms, humans, animals and plants) or synthetically (by the chemical synthesis in laboratories). The role of peptides in nature is very important, because peptides perform a large number of important tasks and irreplaceable functions in living organisms, play a key role in ongoing biological activities and processes. The chemical synthesis of peptides in laboratories can be carried out using classical solution-phase techniques, or using newer, by solid-phase methods. Synthetic peptides may be used in peptide structure or function studies, production of antibodies, peptide hormones or their analogues, to design novel enzymes, drugs or vaccines. At chemical synthesis of peptides in laboratories exists great flexibility for large amount of applications and amino acid sequences. In addition, synthetic peptides can be modified to change their properties or conformation, conjugated to immunogens for antibody, drugs or vaccines production or isotopically labeled for protein quantitation.
Due to the extraordinary importance of peptides in nature, and the great potential and possibilities for their use in many sectors of human activity (including chemical, cosmetic or medical industry), the research of peptides and proteins represents today a very important and extensively investigated area of scientific research. Many scientists and researchers around the world, from amateurs to the best biology research professionals, are making great and intensive efforts to research, develop and study peptides and proteins.
For scientific research we sale first-class peptides, proteins and non-dangerous chemicals of the highest quality, at reasonable prices. We strongly remind you that all of our products we offer are manufactured, intended and sold solely for scientific purposes and research use only, and not for any other purposes. Please note and understand, that despite the fact that scientific studies could find out or to confirm some positive benefits of offered peptides for sale and chemicals for humans, these substances are still yet subject to further intensive scientific research, and they are not yet sufficiently examined for other kind of use as research. From this reason, all our products are strictly intended and sold for scientific purposes only. You can buy peptides, sarms and other research non-dangerous chemicals by us for research use only. Also carefully read our terms and conditions before you order, you must fully agree with them and follow them (what you must too confirm when creating each order), in another case, or if we suspect abuse, we reserve the right to refuse to sell you. If you have any further questions related to peptides sale, their properties or use, please first try read page frequently asked questions, and if you don't find the answer, then please contact us. Thank you for your attention, interest and care, and we wish you much success in your research, peptides sale team. Page content and article written byBrian Davis, research scientist,