NOVEL ENZYMATIC APPROACH TO SEMI-SYNTHESIS OF TAXOL

THE OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE FEASIBILITY OF DEVELOPING AN NOVEL ENZYMATIC PROCESS FOR THE SEMI-SYNTHESIS OF TAXOL. TAXOL IS A PROMISING DRUG FOR TREATMENT OF OVARIAN AND OTHER CANCERS. HOWEVER, IT IS CURRENTLY AVAILABLE ONLY IN LIMITED QUANTITY BY EXTRACTION FROM A RARE TREE; CHEMICAL SYNTHESIS IS DIFFICULT AND IMPRACTICAL. THIS LIMITED AVAILABILITY HAS PREVENTED WIDE-SCALE CLINICAL TESTING FOR EFFICACY AGAINST MANY TYPES OF CANCER. IN THIS PHASE I PROGRAM, THE INVESTIGATORS WILL INVESTIGATE THE USE OF ENZYMES TO PRODUCE TAXOL BY COUPLING THE TAXOL SIDE-CHAIN TO A TAXOL PRECURSOR, WHICH IS READILY OBTAINABLE FROM ORNAMENTAL SHRUBS. THIS COUPLING, OR ACYLATION, STEP IS THE MOST DIFFUCULT STEP IN THE SEMI-SYNTHESIS OF TAXOL FROM ITS PRECURSOR. IF THE RESULTS OF PHASE I ARE PROMISING, THEN EFFORTS IN PHASE II WILL BE AIMED AT INCORPORATING THIS STEP INTO SYNTHESIS SCHEMES FOR TAXOL, AS WELL AS DEVELOPING ENZYMATIC APPROACHES TO OTHER KEY STEPS IN THE SEMI-SYNTHESIS OF TAXOL. THIS PROGRAM COULD LEAD TO COMMERCIALLY ECONOMICAL PRODUCTION OF TAXOL, ENABLING CLINICAL STUDIES FOR OTHER CANCERS TO BE UNDERTAKEN WITH TAXOL WHILE PROVIDING SUFFICIENT QUANTITIES FOR TREATMENT OF CANCER PATIENTS.