Phosphorothioate-modified oligodeoxyribonucleotides. III. NMR and UV spectroscoptc studies of theRp-Rp,Sp-Sp, andRp-Spduplexes, [d(GGsAATTCC)]2, derived from diastereomericO-ethyl phosphorothioates

Abstract

2D—NOE and ¹H NMR chemical shift data obtained for the title oligonucleotides were compared with similar data previously reported [Broido et al. (1985) Hun J. Biochem. 150, 117–128] for the unmodified “parent”structure, [d(GGAAflCC)]₂. The spectroscopically detectable structural perturbations caused by replacement of phosphate oxygen with sulfur were mostly localized within the G_sA moiety, and re greater for the R_p configuration wherein sulfur is oriented into the major groove of the B—helix. UV—derived T_m measurements gave the following order of stability for the duplexes in 0.4 M NaC1: unmodified (33.9±0.1 °C) s_p-s_p (34.1 °C) > (31.7 °C). The title compounds were prepared by a new and convenient synthetic route which utilized HPLC to separate the diastereomeric O—ethyl phosphorothioate precursors, (R_p)— and (S_p)—d[GG(S, EtMflCC), for subsequent de—ethylation by ammonia in water.