Antipain

Antipain is an oligopeptide that is isolated from actinomycetes and used in biochemical research as a protease inhibitor of trypsin and papain.[1] It was discovered in 1972 and was the first natural peptide found that contained an ureylene group.[2] Antipain can aid in prevention of coagulation in blood. It is an inhibitor of serine and cysteine proteases.[3]

This article is about the protease inhbitor. For the article about pain relief, see analgesic.
Antipain
Names
IUPAC name
N2-{[(1S)-1-carboxy-2-phenylethyl]carbamoyl}-N5-(diaminomethylidene)-L-ornithyl-N-{(2S)-5-[(diaminomethylidene)amino]-1-oxopentan-2-yl}-L-valinamide
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • InChI=1S/C27H44N10O6/c1-16(2)21(23(40)34-18(15-38)10-6-12-32-25(28)29)37-22(39)19(11-7-13-33-26(30)31)35-27(43)36-20(24(41)42)14-17-8-4-3-5-9-17/h3-5,8-9,15-16,18-21H,6-7,10-14H2,1-2H3,(H,34,40)(H,37,39)(H,41,42)(H4,28,29,32)(H4,30,31,33)(H2,35,36,43)/t18-,19-,20-,21-/m0/s1 checkY
    Key: SDNYTAYICBFYFH-TUFLPTIASA-N checkY
  • InChI=1/C27H44N10O6/c1-16(2)21(23(40)34-18(15-38)10-6-12-32-25(28)29)37-22(39)19(11-7-13-33-26(30)31)35-27(43)36-20(24(41)42)14-17-8-4-3-5-9-17/h3-5,8-9,15-16,18-21H,6-7,10-14H2,1-2H3,(H,34,40)(H,37,39)(H,41,42)(H4,28,29,32)(H4,30,31,33)(H2,35,36,43)/t18-,19-,20-,21-/m0/s1
    Key: SDNYTAYICBFYFH-TUFLPTIABE
  • O=C[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)N[C@H](C(=O)O)Cc1ccccc1)CCC/N=C(\N)N)C(C)C)CCC/N=C(\N)N
Properties
C27H44N10O6
Molar mass 604.713 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references

It has been crystallised in complexes with carboxypeptidase, which is obtained from wheat,[4] and Leishmania major oligopeptidase B.[5] In both cases, the backbone carbonyl of the terminal arginine of antipain forms a covalent bond to the active site serine in the protease.

In oncology, pain control is an ongoing problem. An important obstacle to controlling cancer pain is related to the patient.[6] A recent research article indicated that antipain Y is a new type of anti-pain analog, which can inhibit the release of neurotransmitter in rat dorsal root ganglion neurons.[7] An experiment focused on potential improvement for pain management of oncology patients with antipain.[8]

A study was performed for information on the effect of antipain on the quality of post-thawed ram semen.[9] The results from this experiment concluded that antipain aided in the quality of ram semen by maintaining the sperm mobility.[10] Antipain includes the function to inhibit a degrading enzyme, called plasmin, permitting this substance to be able to improve the resistance of membrane disruption by freezing temperatures.[10]

Antiretroviral and protease inhibitors

There are several serine proteases, which are enzymes that cleave the protein bond, in the human genome. Proteases are ubiquitous. Protease function is also affected by endogenous inhibitors.[11] The abnormal functioning of these proteases can lead to the development of cancerous tumors.[12][13] Protease inhibitors or antipain are enzymes that are used to regulate their performance.

The antiretroviral drug Nelfinavir is one example of an antipain. It was classified as an antipain after a study published by Ovid that investigated the in vitro effect of Nelfinavir using proteolytic foot printing and found that it selectively inhibited HER2- positive, a growth factor in breast cancer.[14]

Antipain is a reversible inhibitor of trypsin, papain, and, plasmin, which is isolated from actinomycetes.[15]

Protease inhibitors and DRUG neurons

Protease-activated receptors (PARs) are a unique class of G protein-coupled receptors activated by proteolytic cleavage of the receptor N terminus.[16] PARs are activated by some Serine Proteases and are important for the physiological, psychological,[17] and pathological functions of the human body.

During the study, an antipain analogue Y was developed and studied. It was shown to have properties as a protease inhibitors but it had a low IC50 than a antipain. Antipain analogue Y was able to suppress Trypsin, which inhibits the secretion of an excitatory neuropeptide that leads to inflammation and other disorders. Antipain is a protease inhibitor, usually 1–2 μg/mL, and is well-against to cathepsin A, cathepsin B, papain and trypsin protease enzymes.[18]

References
  1. Suda H, Aoyagi T, Hamada M, Takeuchi T, Umezawa H (April 1972). "Antipain, a new protease inhibitor isolated from actinomycetes". The Journal of Antibiotics. 25 (4): 263–266. doi:10.7164/antibiotics.25.263. PMID 4559651.
  2. Umezawa S, Tatsuta K, Fujimoto K, Tsuchiya T, Umezawa H (April 1972). "Structure of antipain, a new Sakaguchi-positive product of streptomyces". The Journal of Antibiotics. 25 (4): 267–270. doi:10.7164/antibiotics.25.267. PMID 5052959.
  3. Lackie J (2012). A Dictionary of Biomedicine. Oxford University Press. ISBN 9780199549351.
  4. PDB ENTRY 1bcr Bullock TL, Breddam K, Remington SJ (February 1996). "Peptide aldehyde complexes with wheat serine carboxypeptidase II: implications for the catalytic mechanism and substrate specificity". Journal of Molecular Biology. 255 (5): 714–725. doi:10.1006/jmbi.1996.0058. PMID 8636973.
  5. PDB ENTRY 2xe4 McLuskey K, Paterson NG, Bland ND, Isaacs NW, Mottram JC (December 2010). "Crystal structure of Leishmania major oligopeptidase B gives insight into the enzymatic properties of a trypanosomatid virulence factor". The Journal of Biological Chemistry. 285 (50): 39249–39259. doi:10.1074/jbc.M110.156679. PMC 2998157. PMID 20926390.
  6. Koller A, Gaertner J, De Geest S, Hasemann M, Becker G (September 2018). "Testing the Implementation of a Pain Self-management Support Intervention for Oncology Patients in Clinical Practice: A Randomized Controlled Pilot Study (ANtiPain)". Cancer Nursing. 41 (5): 367–378. doi:10.1097/ncc.0000000000000502. PMID 28537957. S2CID 41363992.
  7. Nakae K, Kojima F, Sawa R, Kubota Y, Igarashi M, Kinoshita N, et al. (January 2010). "Antipain Y, a new antipain analog that inhibits neurotransmitter release from rat dorsal root ganglion neurons". The Journal of Antibiotics. 63 (1): 41–44. doi:10.1038/ja.2009.109. PMID 19911027.
  8. Koller A (2018). Testing the Implementation of a Pain Self-management Support Intervention for Oncology Patients in Clinical Practice: A Randomized Controlled Pilot Study (ANtiPain). Wolters Kluwer Health, Inc. pp. 1–18.
  9. "The protease inhibitor antipain has a beneficial synergistic effect with trehalose for ram semen cryopreservation".
  10. The Protease Inhibitor Antipain has a Beneficial Synergistic Effect with Trehalose for Ram Semen Cryopreservation. Germany: Wiley Subscription Services, Inc. 2018. pp. 2–42.
  11. Dhalla NS (2014). Role of Proteases in Cellular Dysfunction. New York, NY : Springer New York : Imprint: Springer. pp. 3–15.
  12. Quesada V, Ordóñez GR, Sánchez LM, Puente XS, López-Otín C (January 2009). "The Degradome database: mammalian proteases and diseases of proteolysis". Nucleic Acids Research. 37 (Database issue): D239–D243. doi:10.1093/nar/gkn570. PMC 2686449. PMID 18776217.
  13. Mariño G, Uría JA, Puente XS, Quesada V, Bordallo J, López-Otín C (February 2003). "Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy". The Journal of Biological Chemistry. 278 (6): 3671–3678. doi:10.1074/jbc.M208247200. PMID 12446702.
  14. Shim JS, Rao R, Beebe K, Neckers L, Han I, Nahta R, Liu JO (October 2012). "Selective inhibition of HER2-positive breast cancer cells by the HIV protease inhibitor nelfinavir". Journal of the National Cancer Institute. 104 (20): 1576–1590. doi:10.1093/jnci/djs396. PMC 3472971. PMID 23042933.
  15. "Antipain", Encyclopedic Dictionary of Genetics, Genomics and Proteomics, Hoboken, NJ, USA: John Wiley & Sons, Inc., 2004-07-15, doi:10.1002/0471684228.egp00764, ISBN 0-471-68422-8, retrieved 2021-03-29
  16. Nakae K, Kojima F, Sawa R, Kubota Y, Igarashi M, Kinoshita N, et al. (January 2010). "Antipain Y, a new antipain analog that inhibits neurotransmitter release from rat dorsal root ganglion neurons". The Journal of Antibiotics. 63 (1): 41–44. doi:10.1038/ja.2009.109. PMID 19911027.
  17. Nakae K, Saito K, Iino T, Yamamoto N, Wakabayashi M, Yoshikawa S, et al. (December 2005). "A prostacyclin receptor antagonist inhibits the sensitized release of substance P from rat sensory neurons". The Journal of Pharmacology and Experimental Therapeutics. 315 (3): 1136–1142. doi:10.1124/jpet.105.091967. PMID 16109742. S2CID 14841421.
  18. "Antipain", Encyclopedia of Genetics, Genomics, Proteomics and Informatics, Dordrecht: Springer Netherlands, 2008, p. 120, doi:10.1007/978-1-4020-6754-9_957, ISBN 978-1-4020-6753-2, retrieved 2021-03-29


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