NUCLEOSIDE PHOSPHATE ANALOGUES WITH BORONATED PHOSPHATES

USE OF NUCLEOSIDE PHOSPHATES AS ANTITUMOR AND ANTIVIRAL AGENTS HAS BEEN LIMITED BY THEIR INABILITY TO PENETRATE CELL MEMBRANES AS WELL AS THEIR HIGH SUSCEPTIBILITY TO ENZYMES SUCH AS PHOSPHATASES, NUCLEOTIDASES, ETC. MODIFICATION OF THE PHOSPHATE GROUP (BY REPLACING ONE OF THE NONBRIDGING OXYGENS WITH A BORANE GROUP) MAY PROVIDE BOTH THE MEMBRANE PERMEABILITY TO THESE COMPOUNDS AND THE STABILITY (TOWARDS PHOSPHATE-REMOVING ENZYMES). THE LONG- TERM OBJECTIVE OF THIS PROJECT IS TO SYNTHESIZE NUCLEOSIDE MONO-, DI- AND TRIPHOSPHATES IN WHICH ONE OF THE OXYGENS OF \, A OR G PHOSPHORUS HAS BEEN REPLACED WITH AN ISOELECTRONIC BORANE GROUP. THESE COMPOUNDS MAY BE PREPARED BY PHOSPHORYLATION OF NUCLEOSIDES, NUCLEOSIDE MONOPHOSPHATES AND NUCLEOSIDE DIPHOSPHATES USING A BORONATED PHOSPHORYLATING AGENT. IN OUR STUDIES WITH RELATED OLIGONUCLEOTIDE BORANOPHOSPHATES, THE P-BH3 MOIETY HAS BEEN FOUND TO BE REMARKABLY STABLE AND THE OLIGONUCLEOTIDE BORANOPHOSPHATES HAVE HIGH NUCLEASE RESISTANCE. THE NUCLEOSIDE BORANOPHOSPHATES MAY BE USEFUL IN A NUMBER OF WAYS INCLUDING: 1) AS TOOLS FOR STUDYING MECHANISM OF ACTION OF ENZYMES, 2) AS ANTIVIRAL AND ANTITUMOR AGENTS, AND 3) AS CARRIERS OF BORON FOR BORON NEUTRON CAPTURE THERAPY.