AN OLIGODEOXYRIBONUCLEOTIDE N3'-]P5' PHOSPHORAMIDATE DUPLEX FORMS AN A-TYPE HELIX IN SOLUTION

The solution conformations of the dinucleotide d(TT) and the modified duplex d(CGCGAATTCGCG)(2) with N3'-->P5' phosphoramidate internucleosi de linkages have been studied using circular dichroism (CD) and NMR sp ectroscopy. The CD spectra indicate that the duplex conformation is si milar to that of isosequential phosphodiester RNA, an A-type helix, an d is different from that of DNA, a B-type helix. NMR studies of model dimers d(TpT) and N3'-->P5' phosphoramidate d(TnpT) show that the suga r ring conformation changes from predominantly C2'-endo to C3'-endo wh en the 3'-phosphoester is replaced by a phosphoramidate group, Two-dim ensional NMR (NOESY, DQF-COSY and TOCSY spectral studies of the duplex provide additional details about the A-type duplex conformation of th e oligonucleotide phosphoramidate and confirm that all furanose rings of 3'-aminonucleotides adopt predominantly N-type sugar puckering.