Interaction of dolastatin 10 with bovine brain tubulin.
Dolastatin 10 is an unusual peptide of marine origin which binds to tubulin in the vinblastine/maytansine/phomopsin-binding region and potently inhibits mitosis. Using N,N'-ethylenebis(iodoacetamide) (EBI) and iodo[14C]acetamide as probes for the effects of ligands on the thiol groups of tubulin, we found that dolastatin 10 has effects on the sulfhydryls indistinguishable from those of phomopsin A but quite different from those of vinblastine and maytansine. Using the binding of bis-5,5'-[8-(N-phenyl)aminonaphthalene-1-sulfonic acid] (BisANS) as a measure of tubulin decay, we found that dolastatin 10 resembled phomopsin A in that decay was not detectable by this assay in its presence. Interestingly, both otherwise very different peptides are among the most effective inhibitors of tubulin decay yet discovered.
Ludueña
R F
RF
Department of Biochemistry, University of Texas Health Science Center, San Antonio.
Roach
M C
MC
Prasad
V
V
Pettit
G R
GR
D000478:Alkylation; D000817:Anilino Naphthalenesulfonates; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001923:Brain Chemistry; D002417:Cattle; D003432:Cross-Linking Reagents; D003553:Cystine / Q000737:chemistry; D047630:Depsipeptides; D005029:Ethylenediamines; D008870:Microtubules / Q000737:chemistry; D009183:Mycotoxins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D011487:Protein Conformation; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry*; D014747:Vinblastine / Q000494:pharmacology
D000817:Anilino Naphthalenesulfonates; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D047630:Depsipeptides; D005029:Ethylenediamines; D009183:Mycotoxins; D009842:Oligopeptides; D013438:Sulfhydryl Compounds; D014404:Tubulin; D003553:Cystine; D014747:Vinblastine; C035763:5,5'-bis(8-(phenylamino)-1-naphthalenesulfonate); C035753:phomopsin; C032156:N,N'-ethylenebis(iodoacetamide); C064570:dolastatin 10