STEREODIFFERENTIATION - THE EFFECT OF P CHIRALITY OF OLIGO(NUCLEOSIDEPHOSPHOROTHIOATES) ON THE ACTIVITY OF BACTERIAL RNASE-H

P stereoregular phosphorothioate analogs of pentadecamer 5'-d(AGATGTTT GAGCTCT)-3' were synthesized by the oxathiaphospholane method. Their d iastereomeric purity was assigned by means of enzymatic degradation wi th nuclease P1 and, independently, with snake venom phosphodiesterase. DNA-RNA hybrids formed by phosphorothioate oligonucleotides (PS-oligo s) with the corresponding complementary pentadecaribonucleotide were t reated with bacterial RNase H. The DNA-RNA complex containing the PS-o ligo of [all-R(p)] configuration was found to be more susceptible to R Nase H-dependent degradation of the pentadecaribonucleotide compared w ith hybrids containing either the [all-Sp] counterpart or the so calle d 'random mixture of diastereomers' of the pentadeca(nucleoside phosph orothioate). This stereodependence of RNase H action was also observed for a polyribonucleotide (475 nt) hybridized with these phosphorothio ate oligonucleotides. The results of melting studies of PS-oligo-RNA h ybrids allowed a rationalization of the observed stereodifferentiation in terms of the higher stability of heterodimers formed between oligo ribonucleotides and [all-R(p)]-oligo(nucleoside phosphorothioates), co mpared with the less stable heterodimers formed with [all-S-p]-oligo(n ucleoside phosphorothioates) or the random mixture of diastereomers.