AN APPROACH TO THE STRUCTURE DETERMINATION OF NUCLEIC-ACID ANALOGS HYBRIDIZED TO RNA - NMR-STUDIES OF A DUPLEX BETWEEN 2'-OME RNA AND AN OLIGONUCLEOTIDE CONTAINING A SINGLE AMIDE BACKBONE MODIFICATION

The backbone modification amide-3, in which -CH2-NH-CO-CH2- replaces -C5'H-2-O5'-PO2-O3'-, is studied in the duplex d(G(1)-C-2-G(3)-T-4.T-5-G(6)-C-7-G(8))* mr(C-9-G(10)-C-11-A(12)-A(13)-C-14-G(15)-C-16) where. indicates the backbone modification and mr indicates the 2'-OMe RNA strand. The majority of the exchangeable and non-exchangeable resonances have been assigned. The assignment procedure differs from standard methods. The methyl substituent of the 2'-OMe position of the RNA strand can be used as a tool in the interpretation. The duplex structure is a right-handed double helix. The sugar conformations of the 2'-OMe RNA strand are predominantly N-type and the 2'-OMe is positioned at the surface of the minor groove. In the complementary strand, only the sugar of residue T-4 is found exclusively in N-type conformation. The incorporation of the amide modification does not effect very strongly the duplex structure. All bases are involved in Watson-Crick base pairs.