NOVEL BASE BORONATED OLIGONUCLEOTIDES FOR BORON NEUTRON CAPTURE THERAPY

BORON NEUTRON CAPTURE THERAPY (BNCT) HAS A CLEAR THEORETICALADVANTAGE OVER OTHER TECHNIQUES AS A METHOD OF DELIVERING CELL KILLING RADIATION TO TUMORS. NEW BORON COMPOUNDS ARE NEEDED THAT CAN SELECTIVELY LOCALIZE IN TUMORS AND, UPON CAPTURE OF THERMAL OR EPITHERMAL NEUTRONS, PRODUCE RADIATIONTO KILL TUMOR CELLS BUT SPARE NORMAL TISSUE AND BLOOD. BNCTEFFECTIVENESS WOULD BE GREATEST IF THE BORON TARGETED THE CELL NUCLEUS AND LOWER CONCENTRATIONS COULD BE USED. PHASE I WILL SYNTHESIZE BORONATED OLIGONUCLEOTIDES THAT ARE RESISTANT TO NUCLEASES AND THAT SHOULD READILY ENTER CELLS AND TARGET (BY AN "ANTISENSE" MECHANISM) THE DNA OR RNA NUCLEAR MATERIAL OF TUMOR CELLS. THE OLIGONUCLEOTIDES WILL BE PREPARED BOTH CHEMICALLY AND ENZYMATICALLY USING NUCLEOSIDES THAT HAVE BEEN BORONATED ON BASE POSITIONS, AFFECTING BASE PAIRING ABILITIES AND OTHER NORMAL ACTIVITY ONLY MINIMALLY (IF AT ALL). OF CONSIDERABLE ADDED VALUE IS THE EXPECTED ANTI-TUMOR ACTIVITY OF THE BORONATED OLIGONUCLEOTIDES IN ADDITION TO THAT PROVIDED BY BNCT.