1. Interactions of laulimalide, peloruside, and their derivatives with the isoforms of β-tubulin.
- Author
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Gajewski, Melissa M., Tuszynski, Jack A., Barakat, Khaled, Huzil, J. Torin, and Klobukowski, Mariusz
- Subjects
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MOLECULAR structure , *MOLECULAR dynamics , *TUBULINS , *CHEMICAL affinity , *CHEMICAL reactions , *CHEMICAL kinetics - Abstract
The investigational anticancer agents laulimalide and peloruside are known to exert an antimitotic effect on cells by binding to β-tubulin. The binding affinities of derivatives of laulimalide and peloruside to all known isoforms of human β-tubulin were calculated using molecular mechanical, molecular dynamical, and quantum mechanical methods. Several of the derivatives are predicted to have improved β-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 β-tubulin isoforms, which are overexpressed in certain tumours. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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