Mechanistic Studies of Taxadiene and Abietadiene Synthases

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...

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Bibliographic Details
Main Author: Siepmann, Thomas J
Format: Report
Language:English
Subjects:
ABIETADIENE SYNTHASE
ANALOGS
ANTIBIOTICS
ASSAYING
Biochemistry
BREAST CANCER
CHEMOTHERAPY
COMBINATORIAL ANALYSIS
DRUGS
ENZYMES
HYDROCARBONS
MECHANISTIC STUDIES
Medicine and Medical Research
SYNTHASES
TAXADIENE SYNTHASE
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Summary: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.