CELLULAR PHARMACOLOGY AND PROTEIN-BINDING OF PHOSPHOROMONOTHIOATE ANDPHOSPHORODITHIOATE OLIGODEOXYNUCLEOTIDES - A COMPARATIVE-STUDY

Phosphorodithioate (PS2) oligodeoxynucleotides (oligos) represent a re latively new class of backbone-modified oligo that have potential use as antisense agents. PS2 oligos are isoelectronic with phosphodiester (PO) and phosphoromonothioate (PS) oligos, and are nuclease resistant. However, unlike their PS congeners, PS2 oligos do not contain chiral centers. Little is known about the manner in which PS2 oligos interact with biological systems. In this study, we compare the cellular pharm acology of PS and PS2 oligos in HL60 cells. Cell surface binding, inte rnalization, and compartmentalization are examined. Furthermore, the a bility of PS and PS2 oligos to bind to rsCD4 and bFGF and to inhibit t he activity of protein kinase C (PKC) is examined. Although the behavi or of PS2 oligos closely parallels that of PS oligos, PS2 oligos appea r to interact with some biological systems in a slightly different man ner than PS oligos. These results indicate that PS2 oligos may have th erapeutic potential other than as antisense agents.