Interaction of cryptophycin 1 with tubulin and microtubules

FEBS Letters

Schwartz, Robert E.²  Georg, Gunda I.³  Kerksiek, Kristen¹  Mejillano, Marisan R.¹  Himes, Richard H.¹ 

[1] Department of Biochemistry, University of Kansas, Lawrence, KS 66045, USA;Merck, Sharp & Dohme Research Laboratories, Rahway, NJ 07065, USA;Department of Medical Chemistry, University of Kansas, Lawrence, KS 66045, USA

关键词: Cryptophycin;    Vinblastine;    Tubulin;    Antimitotic drug;    PEM buffer;    0.1 M piperazinediethanesulfonate;    1 mM ethyleneglycol bis(β-minoethyl ether)-N;    N N′;    N′-tetraacetic acid 1 mM MgSO4;    pH 6.9;    DMSO;    dimethylsulfoxide;    VLB;    vinblastine;   

DOI  :  10.1016/0014-5793(95)01271-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The cryptophycins are newly discovered antimitotic agents isolated from the cyanobacterium Nostoc. Previous studies using cultured cells demonstrated that microtubules are the target of these compounds. We have studied the interaction of cryptophycin 1 with tubulin and microtubules in vitro. Cryptophycin 1 is an effective inhibitor of tubulin polymerization, causes tubulin to aggregate, and depolymerizes microtubules to linear polymers somewhat similar to the spiral-like structures produced by the Vinca alkaloids. Cryptophycin 1 also inhibits vinblastine binding to tubulin but not colchicine binding. Thus, it appears that the cryptophycins may bind to the Vinca site in tubulin or to a site that overlaps with the Vinca site.

【 授权许可】

Unknown