Dermorphin

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Dermorphin
Dermorphin.svg
Dermorphin 3D spacefill.png
Names
Other names
Tyrosyl-alanyl-phenylalanyl-glycyl-tyrosyl-prolyl-serinamide
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
UNII
  • InChI=1S/C40H50N8O10/c1-23(44-37(55)29(41)18-25-9-13-27(50)14-10-25)36(54)46-30(19-24-6-3-2-4-7-24)38(56)43-21-34(52)45-31(20-26-11-15-28(51)16-12-26)40(58)48-17-5-8-33(48)39(57)47-32(22-49)35(42)53/h2-4,6-7,9-16,23,29-33,49-51H,5,8,17-22,41H2,1H3,(H2,42,53)(H,43,56)(H,44,55)(H,45,52)(H,46,54)(H,47,57)/t23-,29+,30+,31+,32+,33+/m1/s1 X mark.svgN
    Key: FHZPGIUBXYVUOY-VWGYHWLBSA-N X mark.svgN
  • InChI=1/C40H50N8O10/c1-23(44-37(55)29(41)18-25-9-13-27(50)14-10-25)36(54)46-30(19-24-6-3-2-4-7-24)38(56)43-21-34(52)45-31(20-26-11-15-28(51)16-12-26)40(58)48-17-5-8-33(48)39(57)47-32(22-49)35(42)53/h2-4,6-7,9-16,23,29-33,49-51H,5,8,17-22,41H2,1H3,(H2,42,53)(H,43,56)(H,44,55)(H,45,52)(H,46,54)(H,47,57)/t23-,29+,30+,31+,32+,33+/m1/s1
    Key: FHZPGIUBXYVUOY-VWGYHWLBBR
  • C[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CO)C(=O)N)NC(=O)[C@H](CC4=CC=C(C=C4)O)N
Properties
C40H50N8O10
Molar mass 802.886 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Dermorphin is a hepta-peptide first isolated from the skin of South American frogs belonging to the genus Phyllomedusa . [1] The peptide is a natural opioid that binds as an agonist with high potency and selectivity to mu opioid receptors. [2] [3] Dermorphin is about 30–40 times more potent than morphine, but theoretically may be less likely to produce drug tolerance and addiction due to its high potency. [4] The amino acid sequence of dermorphin is H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2.

Dermorphin is not found in humans or other mammals and similar D-amino acid peptides have only been found in bacteria, amphibians, and molluscs. [5] Dermorphin appears to be made in these through an unusual posttranslational modification carried out by an amino acid isomerase. [6] This unusual process is needed because the D-alanine in this peptide is not among the 20 amino acids coded for in the genetic code and thus the peptide cannot be synthesized in the usual way from the encodings in the genome of an organism.

Illicit use

Dermorphin has been illegally used in horse racing as a performance-enhancing drug. Due to dermorphin's painkilling activity, horses treated with dermorphin may run harder than they would otherwise. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Post-translational modification</span> Chemical changes in proteins following their translation from mRNA

In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA into polypeptide chains, which may then change to form the mature protein product. PTMs are important components in cell signalling, as for example when prohormones are converted to hormones.

Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neoendorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of "big dynorphin". "Big dynorphin" is a 32-amino acid molecule consisting of both dynorphin A and dynorphin B.

β-Endorphin Peptide hormone in humans

β-Endorphin (beta-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin.

<span class="mw-page-title-main">Gastrin-releasing peptide</span>

Gastrin-releasing peptideGRP, is a neuropeptide, a regulatory molecule encoded in the human by the GRP gene. GRP has been implicated in a number of physiological and pathophysiological processes. Most notably, GRP stimulates the release of gastrin from the G cells of the stomach.

<span class="mw-page-title-main">Opioid peptide</span> Class of peptides that bind to opioid receptors

Opioid peptides or opiate peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but they all resemble those of opiates. Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, control of food intake, and the rewarding effects of alcohol and nicotine.

Physalaemin is a tachykinin peptide obtained from the Physalaemus frog, closely related to substance P. Its structure was first elucidated in 1964.

<span class="mw-page-title-main">Kassinin</span> Chemical compound

Kassinin is a peptide derived from the Kassina frog. It belongs to tachykinin family of neuropeptides. It is secreted as a defense response, and is involved in neuropeptide signalling.

<i>Phyllomedusa bicolor</i> Species of amphibian

Phyllomedusa bicolor, the giant leaf frog, bicolor tree-frog, giant monkey frog, or waxy-monkey treefrog, is a species of leaf frog. It can be found in the Amazon basin of Brazil, Colombia (Amazonas), Bolivia, and Peru, and can also be found in the Guianan Region of Venezuela and the Guianas, and in Cerrado of the state of Maranhão in Brazil.

Dermaseptins are a family of peptides isolated from skin of the frog genus Phyllomedusa. The sequence of the dermaseptins varies greatly but due to the presence of lysine residues all are cationic and most have the potential to form amphipathic helices in water or when integrated with the lipid bilayer of the bacterial membrane. Clear separation of two lobes of positive and negative intramolecular electrostatic potential is thought to be important in cytotoxic activity. Dermaseptins are typically 27-34 amino acid residues in length and were the first vertebrate peptides demonstrated as having a lethal effect on the filamentous fungi implicated in severe opportunistic infections accompanying immunodeficiency syndrome and immunosuppressive drug therapy.

<span class="mw-page-title-main">Dynorphin B</span> Chemical compound

Dynorphin B, also known as rimorphin, is a form of dynorphin and an endogenous opioid peptide with the amino acid sequence Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr. Dynorphin B is generated as a proteolytic cleavage product of leumorphin, which in turn is a cleavage product of preproenkephalin B (prodynorphin).

Bombesin-like peptides comprise a large family of peptides which were initially isolated from amphibian skin, where they stimulate smooth muscle contraction. They were later found to be widely distributed in mammalian neural and endocrine cells.

<span class="mw-page-title-main">Vittorio Erspamer</span>

Vittorio Erspamer was an Italian pharmacologist and chemist, known for the identification, synthesis and pharmacological studies of more than sixty new chemical compounds, most notably serotonin and octopamine.

<span class="mw-page-title-main">Tynorphin</span> Synthetic opioid chemical compound

Tynorphin is a synthetic opioid peptide which is a potent and competitive inhibitor of the enkephalinase class of enzymes which break down the endogenous enkephalin peptides. It specifically inactivates dipeptidyl aminopeptidase III (DPP3) with very high efficacy, but also inhibits neutral endopeptidase (NEP), aminopeptidase N (APN), and angiotensin-converting enzyme (ACE) to a lesser extent. It has a pentapeptide structure with the amino acid sequence Val-Val-Tyr-Pro-Trp (VVYPW).

<span class="mw-page-title-main">Biphalin</span> Chemical compound

Biphalin is a dimeric enkephalin endogenous peptide (Tyr-D-Ala-Gly-Phe-NH)2 composed of two tetrapeptides derived from enkephalins, connected 'tail-to-tail' by a hydrazide bridge. The presence of two distinct pharmacophores confers on biphalin a high affinity for both μ and δ opioid receptors (with an EC50 of about 1–5 nM for both μ and δ receptors), therefore it has analgesic activity. Biphalin presents a considerable antinociceptive profile. In fact, when administered intracerebroventricularly in mice, biphalin displays a potency almost 7-fold greater than that of the ultra-potent alkaloid agonist, etorphine and 7000-fold greater than morphine; biphalin and morphine were found to be equipotent after intraperitoneal administration. The extraordinary in vivo potency shown by this compound is coupled with low side-effects, in particular, to produce no dependency in chronic use. For these reasons, several efforts have been carried out in order to obtain more information about structure-activity relationship (SAR). Results clearly indicate that, at least for μ receptor binding, the presence of two pharmacophores is not necessary; Tyr1 is indispensable for analgesic activity, while replacing Phe at the position 4 and 4' with non-aromatic, but lipophilic amino acids does not greatly change the binding properties and in general 4,4' positions are found to be important to design biphalin analogues with increased potency and modified μ/δ selectivity. The hydrazide linker is not fundamental for activity or binding, and it can be conveniently substituted by different conformationally constrained cycloaliphatic diamine linkers.

Deltorphin I, also known as [D-Ala2]deltorphin I or deltorphin C, is a naturally occurring, exogenous opioid heptapeptide and hence, exorphin, with the amino acid sequence Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2. While not known to be endogenous to humans or other mammals, deltorphin I, along with the other deltorphins and the dermorphins, is produced naturally in the skin of species of Phyllomedusa, a genus of frogs native to South and Central America. Deltorphin possesses very high affinity and selectivity as an agonist for the δ-opioid receptor, and on account of its unusually high blood-brain-barrier penetration rate, produces centrally-mediated analgesic effects in animals even when administered peripherally.

Deltorphin, also known as deltorphin A and dermenkephalin, is a naturally occurring, exogenous opioid heptapeptide and thus, exorphin, with the amino acid sequence Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2. Along with the other deltorphins (such as deltorphin I and deltorphin II) and the dermorphins, deltorphin is endogenous to frogs of the genus Phyllomedusa such as P. bicolor and P. sauvagei where it is produced in their skin, and is not known to occur naturally in any other species. Deltorphin is one of the highest affinity and most selective naturally occurring opioid peptides known, acting as a very potent and highly specific agonist of the δ-opioid receptor.

Modified GRF (1-29) often abbreviated as mod GRF (1-29), originally known as tetrasubstituted GRF (1-29), is a term used to identify a 29 amino acid peptide analogue of growth-hormone-releasing hormone (GHRH), a releasing hormone of growth hormone (GH). It is a modified version of the shortest fully functional fragment of GHRH, often referred to as growth hormone releasing factor (1-29), and also known by its standardized name, sermorelin.

Sauvagine is a neuropeptide from the corticotropin-releasing factor (CRF) family of peptides and is orthologous to the mammalian hormone, urocortin 1, and the teleost fish hormone, urotensin 1. It is 40 amino acids in length, and has the sequence XGPPISIDLSLELLRKMIEIEKQEKEKQQAANNRLLLDTI-NH2, with a pyrrolidone carboxylic acid modification at the N-terminal and amidation of the C-terminal isoleucine residue. It was originally isolated from the skin of the frog Phyllomedusa sauvagii. Given its relation to other CRF-related peptides, it exerts similar physiological effects as corticotropin-releasing hormone.

<span class="mw-page-title-main">Kambo (drug)</span> Pseudoscientific use of tree frog secretions

Kambo, also known as sapo or vacina-do-sapo, is substance derived from the natural secretions of an amphibian belonging to the Phyllomedusa family. Commonly the dried skin secretions of the giant leaf frog, known as the kambô in Portuguese, a species of frog, are used for ritualistic purposes with a strong religious and spiritual components. Less commonly it is used as a transdermal medicine, however, evidence for its effectiveness is limited.

References

  1. Melchiorri P, Negri L (1996). "The dermorphin peptide family". Gen. Pharmacol. 27 (7): 1099–107. doi:10.1016/0306-3623(95)02149-3. PMID   8981054.
  2. Amiche M, Delfour A, Nicolas P (1998). "Opioid peptides from frog skin". D-Amino Acids in Sequences of Secreted Peptides of Multicellular Organisms. Vol. 85. pp. 57–71. doi:10.1007/978-3-0348-8837-0_4 (inactive 2024-09-12). ISBN   978-3-0348-9794-5. PMID   9949868.{{cite book}}: |journal= ignored (help)CS1 maint: DOI inactive as of September 2024 (link)
  3. Erspamer V, Melchiorri P, Falconieri-Erspamer G, et al. (1989). "Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites". Proc. Natl. Acad. Sci. U.S.A. 86 (13): 5188–92. Bibcode:1989PNAS...86.5188E. doi: 10.1073/pnas.86.13.5188 . PMC   297583 . PMID   2544892.
  4. Broccardo M, Erspamer V, Falconieri Erspamer G, et al. (1981). "Pharmacological data on dermorphins, a new class of potent opioid peptides from amphibian skin". Br. J. Pharmacol. 73 (3): 625–31. doi:10.1111/j.1476-5381.1981.tb16797.x. PMC   2071698 . PMID   7195758.
  5. Kreil G (15 April 1994). "Peptides containing a D-amino acid from frogs and molluscs". J. Biol. Chem. 269 (15): 10967–70. doi: 10.1016/S0021-9258(19)78075-2 . PMID   8157620.
  6. Heck SD, Faraci WS, Kelbaugh PR, Saccomano NA, Thadeio PF, Volkmann RA (1996). "Posttranslational amino acid epimerization: enzyme-catalyzed isomerization of amino acid residues in peptide chains". Proc. Natl. Acad. Sci. U.S.A. 93 (9): 4036–9. Bibcode:1996PNAS...93.4036H. doi: 10.1073/pnas.93.9.4036 . PMC   39482 . PMID   8633012.
  7. Bogdanich W (19 June 2012). "Turning to Frogs for Illegal Aid in Horse Races". New York Times. Retrieved 19 June 2012.