Interactions of laulimalide, peloruside, and their derivatives with the isoforms of β-tubulin

The investigational anticancer agents laulimalide and peloruside are known to exert an antimitotic effect on cells by binding to beta-tubulin. The binding affinities of derivatives of laulimalide and peloruside to all known isoforms of human beta-tubulin were calculated using molecular mechanical, molecular dynamical, and quantum mechanical methods. Several of the derivatives are predicted to have improved beta-tubulin binding affinities compared to the parent structures. These results can form the starting point for developing laulimalide or peloruside derivatives with greater specificity for the particular beta-tubulin isoforms, which are overexpressed in certain tumours.