Interactions of the catharanthus (Vinca) alkaloids with tubulin and microtubules

doi:10.1016/0163-7258(91)90081-V

Pharmacology & Therapeutics

Volume 51, Issue 2, 1991, Pages 257-267

https://doi.org/10.1016/0163-7258(91)90081-V Get rights and content

Abstract

The dimeric Vinca alkaloids present a group of important anti-tumor compounds whose intracellular target is tubulin, the protein monomer of microtubules. In this review data on the binding of these drugs to tubulin and microtubules in vitro are examined. The binding to tubulin is linked to a protein self-association reaction described by Na and Timasheff (1986a) as a ligand-induced plus ligand-mediated isodesmic self-association reaction. The simplest model which fits the binding data is one in which there is one intrinsic site which is linked to the self-association process. Effects of solution variables on the binding and self-association explain the wide variation of reported apparent binding constants for Vinca alkaloids to tubulin. The Vinca drugs also bind to microtubules via a low number of sites at the ends of microtubules with apparent high affinity and which are involved in the inhibition of tubulin dimer addition to the microtubule ends, and to sites along the microtubule wall with apparent low affinity which are involved in the disruption of the microtubules into spiraled protofilaments. This review also compares available binding data for different natural and semi-synthetic Vinca alkaloids.

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Interactions of the catharanthus (Vinca) alkaloids with tubulin and microtubules

Abstract

J. molec. Biol.

Biochem. Pharmac.

Expl. Cell Res.

J. molec. Biol.

J. molec. Biol.

J. biol. Chem.

J. biol. Chem.

J. biol. Chem.

Biochem. biophys. Res. Commun.

Biochem. Pharmac.

J. biol. Chem.

J. biol. Chem.

Biochem. Pharmac.

J. molec. Biol.

J. molec. Biol.

Microtubular crystals in mammalian cells

J. Cell Biol.

Induction in vitro of microtubular crystals by Vinca alkaloids

Science

Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites

Definition of three classes of binding sites in isolated microtubule crystals

Biochemistry

Structure-activity relationships of dimeric Catharanthus alkaloids. 2. Experimental antitumor activities of N-substituted deacetylvinblastine amide (vindesine sulfates)

J. med. Chem.

Biological properties of vincaleukoblastine, an alkaloid in Vinca rosea Linn, with reference to its antitumor action

Cancer Res.

Effect of microtubule-associated proteins on the interaction of vincristine with microtubules and tubulin

Cancer Res.

Negatively stained vinblastine aggregates

Ann. N.Y. Acad. Sci.

Magnesium-induced self-association of calf brain tubulin. I. Stoichiometry

Biochemistry

Magnesium-induced self-association of calf brain tubulin. II. Thermodynamic

Biochemistry

Substructural analysis of the microtubule and its polymorphic forms

Ann. N.Y. Acad. Sci.

Effects of vincristine on the fine structure of HeLa cells during mitosis

J. natn. Cancer Inst.

Dimeric Catharanthus alkaloids

Spirals and paracrystals induced by vinca alkaloids: evidence that microtubule-associated proteins act as polycations

J. Cell. Sci.

Antitumor principles derived from Vinca rosea Linn. I. Vincaleukoblastine and leurosine

Cancer Res.