64925-80-0

Usage

Uses

Used in Pharmaceutical Applications:
PHOMOPSIN A is used as a potent microtubule inhibitor for its ability to selectively bind to dimeric tubulin, overlapping with the sites of vinblastine and maytansine, and inhibiting the formation of the microtubule spindle to block cell division. This property makes it a valuable tool in the development of new therapeutic strategies for various diseases.
Used in Research and Development:
PHOMOPSIN A is used as an important bioprobe for understanding cellular structural proteins, particularly in the study of tubulin and its role in cell division. Its unique ability to protect tubulin from decay makes it a valuable asset in the field of cellular biology and drug discovery.
Used in Agricultural Applications:
PHOMOPSIN A is used as a potent mycotoxin produced by the fungus, Phomopsis leptostromiformis, which causes lupinosis in livestock fed infected lupins. This application is important for understanding the effects of mycotoxins on animal health and for developing strategies to prevent or mitigate the impact of these toxins on livestock and the agricultural industry.

Biological Activity

phomopsin a is a cyclic hexapeptide mycotoxin that inhibits β-tubulin.phomopsins are a family of mycotoxins produced by the fungus phomopsis leptostomiformis grows on lupins, which cause lupinosis, a severe liver disease of grazing animals [1][2].microtubules are one of the major components of the cytoskeleton that are essential in several cellular functions such as cell division and morphogenesis. α- and β-tubulins polymerize into microtubules.phomopsin a is a cyclic hexapeptide mycotoxin that binds β-tubulin in a vinca domain, partly overlapping with the site targeted by vinblastine and other tubulin inhibitors [2][3]. phomopsin a noncompetitively inhibited the binding of radiolabeled vinblastine to tubulin with ic50 and ki values of 0.8 μm and 2.8 μm, respectively. phomopsin a potently inhibited tubulin-dependent gtp hydrolysis and nucleotide exchange on tubulin [2]. phomopsin a, a vinca domain antimitotic peptide, also inhibited microtubule assembly [3][4]. phomopsin a inhibited microtubule growth, modulated the dynamics of microtubules, and induced the self-association of tubulin dimers into single-walled rings and spirals [4].

Enzyme inhibitor

This mycotoxin and antibiotic (FW = 789.24 g/mol; CAS 64925-80-0) is obtained from Diaporthe toxica (formerly Phomopsis leptostromiformis), a fungus that grows mainly within lupin stems, the consumption of which leads to lupinosis in sheep grazing on lupin stubble. Intoxication results in liver damage, disorientation, blindness, lethargy and death in severe cases. Phomopsin A is a 13-membered ether oxygen-containing macrolide that blocks tubulin polymerization (Ki <1 μM). It also inhibits vinblastine binding to tubulin and, in common with vinblastine and maytansine, enhances colchicine binding. Phomopsin A and the depsipeptide, Dolastatin 10, bind to a site adjacent to the vinca alkaloid and nucleotide sites. This mycotoxin induces tubulin oligomerization into ring structures that cannot form microtubules. Scatchard analysis suggests two classes of binding sites: a high-affinity site (K1 = 1 x 10–8 M) and a low-affinity site (K2 = 3 x 10–7 M). Phomopsin A also inhibits rhizoxin binding, with a Ki of 0.8 x 10–8 M, suggesting that the high-affinity site of phomopsin A is identical to the rhizoxin binding site. The development and validation of an LC-MS/MS method for detecting Phomopsin A in lupin and lupincontaining retail food has been reported.

references

[1]. hamel e. natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin a, dolastatins 10 and 15 and halichondrin b. pharmacol ther. 1992;55(1):31-51.[2]. cormier a, marchand m, ravelli rb, et al. structural insight into the inhibition of tubulin by vinca domain peptide ligands. embo rep. 2008 nov;9(11):1101-6.[3]. li y, kobayashi h, hashimoto y, et al. binding selectivity of rhizoxin, phomopsin a, vinblastine, and ansamitocin p-3 to fungal tubulins: differential interactions of these antimitotic agents with brain and fungal tubulins. biochem biophys res commun. 1992 sep 16;187(2):722-9.[4]. mitra a, sept d. localization of the antimitotic peptide and depsipeptide binding site on beta-tubulin. biochemistry. 2004 nov 9;43(44):13955-62.

InChI:InChI=1/C36H45ClN6O12/c1-8-17(5)25-32(51)38-20(15-23(45)46)34(53)42(7)26(27(47)18-13-19(37)28(48)22(44)14-18)33(52)39-24(16(3)4)31(50)41-29(36(6,55)9-2)35(54)43-12-10-11-21(43)30(49)40-25/h10-11,13-15,21,24,26-27,29,44,47-48,55H,3,8-9,12H2,1-2,4-7H3,(H,38,51)(H,39,52)(H,40,49)(H,41,50)(H,45,46)/b20-15-,25-17-