STABILITY OF STEREOREGULAR OLIGO(NUCLEOSIDE PHOSPHOROTHIOATE)S IN HUMAN PLASMA - DIASTEREOSELECTIVITY OF PLASMA 3'-EXONUCLEASE

The stability of stereoregular oligo(nucleoside phosphorothioate)s (PS -oligos) in human plasma has been studied. 3'-Exonuclease present in h uman plasma appeared to be R(p) specific, that is, it cleaves internuc leotide phosphorothioate linkages of [R(p)]-configuration and not thos e of [S-p]-configuration. Therefore, PS-oligos containing all phosphor othioate internucleotide linkages of [R(p)]-configuration [R(p)-PS-oli gos]) are more effectively degraded by the enzyme than PS-oligos prepa red via nonstereocontrolled methods (so-called random mixture of diast ereomers [Mix-PS-oligos]), whereas oligo(nucleoside phosphorothioate)s of [S-p]-configuration remain intact. The enzyme activity depends on the sequence of nucleobases. The presence of deoxycytidine units (thre e or more residues) at the 3'-end of PS-oligo substrate significantly inhibits the enzyme activity.