Dissociation of tubulin assembly-inhibiting and aggregation-promoting activities by a vinblastine derivative.
A fluorescent vinblastine analogue, vinblastine-4'-anthranilate (Antvin), that binds to the vinca site on tubulin, inhibits tubulin assembly but does not lead to spiral or other large aggregate formation at concentrations up to 1.6 mM. As judged by turbidity, 90 degrees light scattering and fluorescence anisotropy, little aggregation could be detected. This is in marked contrast to vinblastine and suggests that inhibition of assembly and aggregate formation can be dissociated from each other by suitable substitution in vinblastine.
Rai
S S
SS
Laboratory of Biochemical Pharmacology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Wolff
J
J
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D007700:Kinetics; D008027:Light; D046911:Macromolecular Substances; D015636:Magnesium Chloride / Q000494:pharmacology; D015394:Molecular Structure; D051381:Rats; D012542:Scattering, Radiation; D014404:Tubulin / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000378:metabolism* / Q000494:pharmacology*
D046911:Macromolecular Substances; D014404:Tubulin; D062367:ortho-Aminobenzoates; C099968:vinblastine-4'-anthranilate; D015636:Magnesium Chloride; D014747:Vinblastine