CONFORMATIONAL STUDY OF DNA-RNA DUPLEXES CONTAINING MMI SUBSTITUTED PHOSPHODIESTER LINKAGES BY FTIR SPECTROSCOPY

Six methylene(methylimino) (MMI, Bhat et al. J. Org. Chem., 61, 8186, 1996) linked oligonucleotides a-f ( = MMI linkage; 5'-GCGT*TT*TT*TT*T TTGCG-3') containing various combinations of 2'-O-methyl and 2'-fluor o substituent were synthesized as a model to study the global conforma tional change upon hybridization to the complement RNA. Fourier transf orm infrared (FTIR) spectroscopic technique has been used to study and compare the influence of these modifications on the solution conforma tion of 2'-modified MMI DNA.RNA duplexes. FTIR analysis of the single- stranded RNA (5'-CGCAAAAAAAAAACGC-3') and the modified oligonucleotide s a-f showed that all sugar residues adopted a C3'-endo conformation ( North-type). Stable duplexes were formed when oligonucleotides a-f wer e hybridized to the complement RNA. These duplexes retained the origin al C3'-endo conformation for all sugar residues, hallmark of an A-form of duplex. We postulate that the observed preorganization of the suga r residues and oligonucleotides containing 2'-modified MMI modificatio ns may play an important role in both improving the recognition of RNA target and enhancing the stability of duplex formation with RNA.