Synthesis and pairing properties of oligodeoxynucleotides containing N-7-(purin-2-amine deoxynucleosides)

A general synthesis of the four isomeric N-7-alpha-D-, N-7-beta-D-, N-9-bet a-D-, and N-9-beta-D-(purin-2-amine deoxy nucleoside phosphoramidite) build ing blacks for DNA synthesis is described (Scheme). The syntheses start wit h methyl 3',5'-di-O-acetyl-2'-deoxy-D-ribofuranoside (2) as the sugar compo nent and the N-2-acetyl-protected 6-chloropurin-2-amine 1 as the base precu rsor. N-7-Selectivity was achieved by kinetic control, and N-9-selectivity by thermodynamic control of the nucleosidation reaction. The two N-7-(purin -2-amine deoxynucleosides) were introduced into the center of a decamer DNA duplex, and their pairing preferences were analyzed by UV-melting curves. Both the N-7-alpha-D- and N-7-beta-D-(purin-2-amine nucleotide) units prefe rentially pair with a guanine base within the Watson-Crick pairing regime, with Delta T(m)s of - 6.7 and - 8.7 K, respectively, relative to a C(.)G ba se pair (Fig. 3 and Table 1). Molecular modeling suggests that, in the form er base pair, the purinamine base is rotated into the syn-arrangement and i s able to form three H-bonds with O(6), N(1), and NH2 of guanine, whereas i n the latter base pair, both bases are in the anti-arrangement with two H-b onds between the N(3) and NH2 of guanine, and NH2 and N(1) of the purin-2-a mine base (Fig. 4).