Pharmaceutical Research 2012-11-01

Peloruside, laulimalide, and noscapine interactions with beta-tubulin.

Melissa M Gajewski, Laleh Alisaraie, Jack A Tuszynski

Index: Pharm. Res. 29(11) , 2985-93, (2012)

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Abstract

This article reviews the recent findings regarding the binding sites, binding modes and binding affinities of three novel antimitotic drugs peloruside, laulimalide and noscapine with respect to tubulin as the target of their action. These natural compounds are shown to bind to β-tubulin and stabilize microtubules for the cases of peloruside A and laulimalide, and prolong the time spent in pause for noscapine. Particular attention is focused on β-tubulin isotypes as targets for new cancer chemotherapy agents and the amino acid differences in the binding site for these compounds between isotypes. We propose a new strategy for antimitotic drug design that exploits differential distributions of tubulin isotypes between normal and cancer cells and corresponding differential affinities between various drug molecules and tubulin isotypes.