N 8 -Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties.

In this report, we present the synthesis of N-8-glycosylated 8-aza-2-methylhypoxanthine and 8-aza-6-thiohypoxanthine 2'-deoxynucleosides as well as methylated 2'-deoxynebularine derivatives. In vitro base pairing properties between each modified and canonical nucleobase were studied. As demonstrated by T-m, incorporation of the modified bases in DNA resulted, with few exceptions, in low stability of duplexes. Modified bases studied in this report are preferentially recognized by T (for N-8-glycosylated 8-aza-2-methylhypoxanthine and methylated purines) and G (N-8-glycosylated 8-aza-2-methylhypoxanthine). The base pair formed between N-8-glycosylated 8-aza-6-thiohypoxanthine and N-9-glycosylated 2-methyl-6-thiohypoxanthine (X2:X6) showed, to some extent, an orthogonal interaction. Based on T-m studies, the only potential self-pairing system is formed by the N-8 -glycosylated 8-aza-6-thiohypoxanthine nucleoside (X2) but only in the absence of canonical G and T. This study indicated that the canonical thymine base is the preferential base partner of methylated purine bases.