Disease relevance of Phomopsin A

• Monoclonal antibody (mAb) C3C11, which recognizes the antimicrotubule phomopsin mycotoxins, was used to isolate peptide mimics of phomopsin A from a random 15-mer phage display peptide library [1].
• It was shown that the different toxic preparations containing similar amounts of phomopsin A varied substantially in toxicity [2].
• Phomopsin, a hexapeptide mycotoxin contaminant of lupin plant and seed materials, was administered subcutaneously to adult rats at a daily dose rate of 30 micrograms/kg body weight (approximately 0.005 median lethal dose) for 2, 6 or 17 wks and the development of liver damage was observed during treatment and for up to 2 yr after [3].

High impact information on Phomopsin A

• Natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B [4].
• Different ligands also differ in their effect on the rate of alkylation of tubulin with iodo[14C]acetamide, with vinblastine and phomopsin A being strong inhibitors and maytansine having very little effect [5].
• Colchicine, vinca alkaloids, dolastatin 10 and phomopsin A induce alternate polymer formation (sheets for colchicine, spirals for vinblastine and vincristine and rings for dolastatin 10 and phomopsin A) [6].
• The macrocyclic heptapeptide, phomopsin A, and the depsipeptide, dolastatin 10, bind to a site adjacent to the vinca alkaloid and nucleotide sites [6].
• Several naturally occurring peptides and depsipeptides which include the cryptophycins, dolastatin 10, hemiasterlin, and phomopsin A have been found to be potent antimitotic agents, causing cell death at picomolar or low nanomolar concentrations [7].

Biological context of Phomopsin A

• This showed that the high affinity site of phomopsin A is identical to the rhizoxin binding site [8].
• The greatest inhibition of hydrolysis was observed with dolastatin 10 and phomopsin A, and the least inhibition with rhizoxin [9].
• Phomopsin A strongly inhibited microtubule assembly (IC50: 2.4 microM) [8].
• The results show that phomopsin A inhibits proliferation by blocking cells in metaphase, but that higher concentrations are needed than for colcemid, another mitotic poison [10].

Associations of Phomopsin A with other chemical compounds

• Like maytansine, phomopsin A completely inhibited formation of a covalent cross-link between cysteines 12 and 201 or 211, induced by N,N'-ethylenebis(iodoacetamide); like vinblastine, phomopsin A strongly inhibited alkylation of tubulin by iodo[14C]acetamide [11].

Gene context of Phomopsin A

• Like vinblastine, phomopsin A stabilizes colchicine binding to tubulin [11].

Analytical, diagnostic and therapeutic context of Phomopsin A

• All four types of phage clones inhibited the reactivity of the mAb with phomopsin A in a competition ELISA [1].

References