FEEDBACK CONTROLLED OLIGONUCLEOTIDE SYNTHESIZER PHASE I

THE INVESTIGATIONS HAVE PROPOSED THE DEVELOPMENT OF AN AUTOMATED OLIGONUCLEOTIDE SYNTHESIZER INCORPORATING A NUMBEROF NEW FEATURES. USING PHOSPHITE-TRIESTER METHODOLOGY FOR OLIGODEOXYRIBONUCLEOTIDE SYNTHESES OCCASIONALLY LOW YIELDS OCCASIONALLY LOW YIELDS ARE OBTAINED IN THE CONDENSATION STEP. THIS PROBLEM CAN BE OVERCOME BY MULTIPLE CONDENSATIONS. HOWEVER, NO ASSAYS ARE CURRENTLY AVAILABLE TO DETERMINE THE EXTENT OF COUPLING IMMEDIATELY FOLLOWING THIS STEP. THE INVESTIGATORS PROPOSE TO DEVELOP AN ANALYTICAL METHOD BASED ON THE COULOMETRIC GENERATION OF IODINE AND SUBSEQUENT STOICHIOMETRIC OXIDATION OF PHOSPHITESTO PHOSPHATES. ELECTROCHEMICAL GENERATION OF A PRECISE QUANTITY OF IODINE WITH ENDPOINT DETERMINATION BY A UV MONITOR WOULD PROVIDE FEEDBACK CONTROL THAT WOULD ALLOW CONDENSATION STEPS TO BE REPEATED WHEN NECESSARY. AUTOMATION AND FEEDBACK CONTROL WOULD BE ACHIEVED THROUGH INTERFACING A NEW TYPE OF REACTOR AND SOLVENT DELIVERY SYSTEM, WITH THE ELECTROCHEMICAL GENERATOR, AND DETECTION SYSTEM, VIA AN APPLE IIE COMPUTER. CONTINUED DEVELOPMENT OF THE REACTION SYSTEM IS PLANNED TO GIVE A UNIT WITH PARALLEL MULTISYNTHESIS CAPABILITIES. A SYSTEM SO CONFIGURED IS PROPOSED TO HAVE THE CAPABILITY OF SYNTHESIZING OLIGOMERS OF GREATER THAN 120 BASES. IMPROVEMENTS PLANNED FOR PHASE II, INCLUDE DEVELOPMENT OF A TUBE REACTOR AND PURIFICATION OF THE OLIGOMER PRODUCTS ON THE SOLID SUPPORT.