A TT Dinucleotide with a Nonionic Silyl Backbone: Impact on Conformation and H-Bond Mediated Base Pairing as Studied by Low-Temperature NMR

摘要

A T_(si)T dinucleotide linked through a nonionic diisopropylsilyl backbone has been synthesized and studied for its self-association through base-base recognition together with a free thymidine nucleoside. To characterize hydrogen-bonded associates in more detail, NMR measurements were performed in a freonic solvent at temperatures as low as 113K in the slow hydrogen bond exchange regime. For the thymidine, TT base pairs with both the 2- and 4-carbonyl engaged in hydrogen bonds to the imino proton were observed. Whereas hydrogen bonds to the 04 acceptor are stronger as evidenced by a more deshielded proton in the hydrogen bridge when compared to hydrogen bonds to the 02 acceptor, the latter is nevertheless slightly favored over 04 in the H-bond formation of TT base pairs. The diisopropylsilyl linkage of the T_(si)T dinucleotide has no significant impact on the geometry and strength of formed NH-O2 and NH-04 hydrogen bonds indicating, that the silyl backbone does not compromise the alignment of bases and does not pose any restrictions to the cyclic hydrogen bond formation between thymidines of the two strands. However, NMR results point to an exclusive formation of T_(si)T duplexes with an antiparallel strand orientation.