• A tetrapeptide is a peptide, classified as an oligopeptide, since it only consists of four amino acids joined by peptide bonds. Many tetrapeptides are pharmacologically active, often showing affinity and specificity for a variety of receptors in protein-protein signaling. Present in nature are both linear and cyclic tetrapeptides (CTPs), the latter of which mimics protein reverse turns which are often present on the surface of proteins and druggable targets
  •  ^{Sage Arbor & Garland R. Marshall (2009). “A virtual library of constrained cyclic tetrapeptides that mimics all four side-chain orientations for over half the reverse turns in the protein data bank”. Journal of Computer-aided Molecular Design. 23 (2): 87–95. doi:10.1007/s10822-008-9241-4. PMID 18797997.}
  •  ^{Sage Arbor, Jeff Kao, Yun Wu & Garland R. Marshall (2008). “c[D-pro-Pro-D-pro-N-methyl-Ala] adopts a rigid conformation that serves as a scaffold to mimic reverse-turns”. Biopolymers. 90 (3): 384–393. doi:10.1002/bip.20869. PMID 17941003.} 
• Tetrapeptides may be cyclized by a fourth peptide bond or other covalent bonds.

Examples of tetrapeptides are:

• Tuftsin (L-threonyl-L-lysyl-L-prolyl-L-arginine) is a peptide related primarily to the immune system function.
• Rigin (glycyl-L-glutaminyl-L-prolyl-L-arginine) is a tetrapeptide with functions similar to those of tuftsin.
• Postin (Lys-Pro-Pro-Arg) is the N-terminal tetrapeptide of cystatin C and an antagonist of tuftsin.
• Endomorphin-1 (H-Tyr-Pro-Trp-Phe-NH₂) and endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH₂) are peptide amides with the highest known affinity and specificity for the μ opioid receptor.
• Morphiceptin (H-Tyr-Pro-Phe-Pro-NH₂) is a casomorphin peptide isolated from β-casein.
• Gluten exorphines A4 (H-Gly-Tyr-Tyr-Pro-OH) and B4 (H-Tyr-Gly-Gly-Trp-OH) are peptides isolated from gluten.
• Tyrosine-MIF-1 (H-Tyr-Pro-Leu-Gly-NH₂) is an endogenous opioid modulator.
• Tetragastrin (N-((phenylmethoxy)carbonyl)-L-tryptophyl-L-methionyl-L-aspartyl-L-phenylalaninamide) is the C-terminal tetrapeptide of gastrin. It is the smallest peptide fragment of gastrin which has the same physiological and pharmacological activity as gastrin.
  • Cholecystokinin tetrapeptide (CCK-4, Trp–Met–Asp–Phe-NH₂) is a peptide fragment derived from the larger peptide hormone cholecystokinin. Unlike cholecystokin which has a variety of roles in the gastrointestinal system as well as central nervous system effects, CCK-4 acts primarily in the brain as an anxiogenic, although it does retain some GI effects, but not as much as CCK-8 or the full length polypeptide CCK-58.
  • CCK-4 reliably causes severe anxiety symptoms when administered to humans in a dose of as little as 50μg,
    •  ^{Eser D, di Michele F, Zwanzger P, Pasini A, Baghai TC, Schüle C, et al. (January 2005). “Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3alpha, 5alpha tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers”. Neuropsychopharmacology. 30 (1): 192–5. doi:10.1038/sj.npp.1300572. PMID 15467707.} 
  • and is commonly used in scientific research to induce panic attacks for the purpose of testing new anxiolytic drugs.
    • Bradwejn J (July 1993). “Neurobiological investigations into the role of cholecystokinin in panic disorder”. Journal of Psychiatry & Neuroscience. 18 (4): 178–88. PMC 1188527. PMID 8104032.
    • Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, et al. (July 2006). “Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety”. NeuroImage. 31 (3): 1197–208. doi:10.1016/j.neuroimage.2006.01.035. PMID 16600640. S2CID 2430104.
    • Eser D, Schüle C, Baghai T, Floesser A, Krebs-Brown A, Enunwa M, et al. (July 2007). “Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept study”. Psychopharmacology. 192 (4): 479–87. doi:10.1007/s00213-007-0738-7. PMID 17318504. S2CID 21457632.
    • Eser D, Leicht G, Lutz J, Wenninger S, Kirsch V, Schüle C, et al. (February 2009). “Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers”. Human Brain Mapping. 30 (2): 511–22. doi:10.1002/hbm.20522. PMC 6870703. PMID 18095276.

• Since it is a peptide, CCK-4 must be administered by injection, and is rapidly broken down once inside the body so has only a short duration of action,
  • ^{Koulischer D, Moroder L, Deschodt-Lanckman M (August 1982). “Degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma in vitro”. Regulatory Peptides. 4 (3): 127–39. doi:10.1016/0167-0115(82)90080-5. PMID 6291099. S2CID 20585962.} 

• See also Pentagastrin

• Kentsin (H-Thr-Pro-Arg-Lys-OH) is a contraceptive peptide first isolated from female hamsters.
• Achatin-I (glycyl-phenylalanyl-alanyl-aspartic acid) is a neuroexcitatory tetrapeptide from giant African snail (Achatina fulica).
• Tentoxin (cyclo(N-methyl-L-alanyl-L-leucyl-N-methyl-trans-dehydrophenyl-alanyl-glycyl)) is a natural cyclic tetrapeptide produced by phytopathogenic fungi from genus Alternaria.
• Rapastinel (H-Thr-Pro-Pro-Thr-NH₂) is a partial agonist of the NMDA receptor.
• HC-toxin, cyclo(D-Pro-L-Ala-D-Ala-L-Aeo), where Aeo is 2-amino-8-oxo-9,10-epoxy decanoic acid, is a virulence factor for the fungus Cochliobolus carbonum on its host, maize.
• Elamipretide, (D-Arg-dimethylTyr-Lys-Phe-NH2) a drug candidate that targets mitochondria.
  •  ^{“Elamipretide”. AdisInsight. Retrieved 24 April 2017.}
  • ^{Kloner, RA; Shi, J; Dai, W (February 2015). “New therapies for reducing post-myocardial left ventricular remodeling”. Annals of Translational Medicine. 3 (2): 20. doi:10.3978/j.issn.2305-5839.2015.01.13. PMC 4322169. PMID 25738140.}

See also

• Dipeptide
• Tripeptide
• Decapeptide
• cyclic peptide

Hormones

Categories: 

• Peptides
• Tetrapeptides
• Protein stubs

From Wikipedia where this page was last updated July 2, 2022