CD, ABSORPTION AND THERMODYNAMIC ANALYSIS OF REPEATING DINUCLEOTIDE DNA, RNA AND HYBRID DUPLEXES [D R(AC)](12)CENTER-DOT[D/R(GT/U)](12) ANDTHE INFLUENCE OF PHOSPHOROTHIOATE SUBSTITUTION/

Circular dichroism (CD) spectra and melting temperature (T-m) data for five duplexes containing phosphorothioate linkages were compared with data for four unmodified duplexes to assess the effect of phosphoroth ioate modification on the structure and stability of DNA DNA and DNA R NA duplexes, Nine duplexes were formed by mixing oligomers 24 nt long in 0.15 M K+ (phosphate buffer), pH 7.0. Unmodified DNA DNA and RNA.RN A duplexes were used as reference B-form and A-form structures, The CD spectra of the modified hybrids S-d(AC)(12).r(GU)(12) and r(AC)(12).S -d(GT)(12) differed from each other but were essentially the same as t he spectra of the respective unmodified hybrids. They were more A-form than B-form in character, CD spectra of duplexes S-d(AC)(12).d(GT)(12 ) and d(AC)(12).S-d(GT)(12) were similar to that of d(AC)(12).d(GT)(12 ), except for a reduced long wavelength CD band, Sulfur modifications on both strands of the DNA duplex caused a pronounced effect on its CD spectrum, The order of thermal stability was: RNA.RNA > DNA.DNA > DNA .RNA, S-DNA.DNA > S-DNA.RNA > S-DNA.S-DNA. Phosphorothioation of one s trand decreased the melting temperature by 7.8 +/- 0.6 degrees C, rega rdless of whether the substitution was in a hybrid or DNA duplex, Ther modynamic parameters were obtained from a multistate analysis of the t hermal melting profiles, Interestingly, the destabilizing effect of th e phosphorothioate substitution appears to arise from a difference in the entropy upon forming the DNA.DNA duplexes, while the destabilizing effect in the DNA.RNA hybrids appears to come from a difference in en thalpy.