N-7-DNA: Synthesis and base pairing of oligonucleotides containing N-7-(2-deoxy-beta-D-erythro-pentofuranosyl)guanine (N(7)G(d))

Abstract

The synthesis of oligonucleotides containing N-7-(2-deoxy-beta-D-erythro-pentofuranosyl)guanine (N(7)G(d); 1) is described. Compound 1 was prepared by nucleobase-anion glycosylation of 2-amino-6-methoxypurine (5) with 2-deoxy-3,5-di-O-(toluoyl)-alpha-D-erythro-pentofuranosyl chloride (6) followed by detoluoylation and displacement of the MeO group (8-->10-->1). Upon base protection with the (dimethylamino)methylidene residue (-->11) the 4,4-dimethoxytrityl group was introduced at OH--C(5')(-->12). The phosphonate 3 and the phosphoramidite 4 were prepared and used in solid-phase oligonucleotide synthesis. The self-complementary dodecamer d(N(7)G-C)(6) shows sigmoidal melting. The T-m of the duplex is 40 degrees. This demonstrates that guanine residues linked via N(7) of purine to the phosphodiester backbone are able to undergo base pairing with cytosine.