Mechanistic Studies of Taxadiene and Abietadiene Synthases
Annual summary rept. 1 May 2000-30 Apr 2001
UTAH UNIV SALT LAKE CITY
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Investigation aimed at understanding the enzymatic mechanism of the two diterpene cyclases, taxadiene and abietadiene synthase, may yield an alternative approach to combinatorial chemistry in the search for new and improved chemotherapeutic and antibiotic drugs. Taxadiene synthase catalyses the rate limiting step in the conversion of geranylgeranyl diphosphate to taxol. Taxol Paclitaxel TM Brystol- Myers Squibb and the related cyclic diterpene, taxotere Docetaxel TM Rhone-Poulenc are successfully used as front line chemotherapeutics in the treatment of several types of cancer including breast cancer. Progress has been made in establishing assay conditions for the diterpene cyclase and synthesizing novel substrate analogs to be used in investigation of this class of enzymes.
- Medicine and Medical Research