Docking studies of the binding mode of dictyostatin and its analogs to the taxoid binding site on β - tubulin

CHED 1302

Christopher B. Hackmeyer, chrishack14@comcast.net, Department of Chemistry, Physics, and Engineering, Spring Hill College, 4000 Dauphin Street #463, Mobile, AL 36608 and Billy W. Day, Departments of Pharmaceutical Sciences and of Chemistry, University of Pittsburgh, 10017 BST3, 3501 Fifth Avenue, Pittsburgh, PA 15213.
The division of a cell's contents during mitosis is highly dependent on the dynamic growth and breakdown of microtubules, which are polymers of tubulin. Because quickly dividing cancerous cells are especially susceptible to disruption of this process, many treatments for cancer have targeted microtubules. Hyperstabilization of tubulin polymers leads to cell cycle and the triggering of apoptosis. Agents with this mechanism of action have been successful in many respects, but they do face certain problems, particularly the emergence of resistant tumors. Computer docking simulations were used to examine binding modes of the promising new antimitotic agent dictyostatin and several analogues with wild-type tubulin and a mutated form that is resistant to paclitaxel and some similar drugs. Based on the results, potential protein-ligand interactions are described. These interactions could help explain the resistance of cells expressing this mutant form of tubulin and also facilitate the formulation of hypotheses regarding new agents to synthesize.
 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007