Oligonucleotide Phosphorofluoridates and Fluoridites

Fluoro derivatives of phosphorus are of great importance in the chemistry and biochemistry of both elements. The incorporation of fluorine into biomolecules has frequently resulted in a remarkable change of biological properties. Simple phosphofluoridates and their structural analogs are the classical inhibitors of serine proteases (1a ). It can be envisaged that a combination of nucleoside fragments with the phosphorofluoridate moiety could result in new properties with respect to selectivity of interaction with the active site of the serine hydroxy group. On the other hand, nucleotides containing a P—F linkage when incorporated into oligonucleotides could be used in the studies of biological functions of nucleic acids, including possibilities connected with the chirality of the phosphorofluoridate moiety. New phosphorofluoridate analogs of nucleotides could also be useful in studying the metabolic processes (1b ) by noninvasive NMR imaging techniques taking advantage of 100% abundance of ¹⁹ F nucleus and its high inherent NMR sensitivity.