Conformational Analysis of the Nucleotides A2'-5'A, A2'-5'A2'-5'A and A2'-5'U from Nuclear Magnetic Resonance and Circular Dichroism Studies

Abstract

In recent publications A2''-5''A2''-5''A was found to be an inhibitor of protein synthesis. Conformational analysis of the 2''-5''-linked nucleotides A2''-5''A, A2''-5''A2''-5''A and A2''-5''U is reported. The complete 1H-NMR assignment of the 3 compounds is given. The degree and mode of base-base stacking is extracted from coupling constant data and circular dichroic (CD) spectra at various temperatures. The 2''-5''-nucleotides surprisingly show a much stronger tendency to stack than the 3''-5'' compounds. At 85.degree. C A2''-5''A occurs for about 50% in stacked states. The mode of stacking is different from 3''-5'' ribonucleotides where the sugar rings predominantly adopt an N conformation. A2''-5''U displays an A(S)2''-5''U(N) stacked state. In A2''-5''A mixed modes of stacking, i.e., NN, NS, SN and SS, are proposed to account for the CD and NMR observations.