Hybrid hexanucleotide duplex containing cyclonucleotides and deoxynucleotides: the d(TA) segment can adopt a high anti left-handed double-helical structure

Abstract

It is known that oligonucleotides containing cyclonucleosides with a high anti (intermediate between anti and syn) glycosidic conformation adopt left-handed, single- and double-helical structures [Uesugi, S., Yano, J., Yano, E., & Ikehara, M. (1977) J. Am. Chem. Soc. 99, 2313-2323]. In order to see whether DNA can adopt the high anti left-handed double-helical structure or not, a self-complementary hexanucleotide containing 6,2'-O-cyclocytidine (C(o)), 8,2'-O-cycloguanosine (G(o)), thymidine, and deoxyadenosine, C(o)G(o)dTdAC(o)G(o), was synthesized. Imino proton NMR spectra and the results of nuclear Overhauser effect experiments strongly suggest that C(o)G(o)dTdAC(o)G(o) adopts a left-handed double-helical structure where the deoxynucleoside residues are involved in hydrogen bonding and take a high anti glycosidic conformation. A conformational model of the left-handed duplex was obtained by calculation with energy minimization. Thus it appears that DNA can form a high anti, left-handed double helix under some constrained conditions, which is quite different from that of Z-DNA.