N8-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties.

In this report, we present the synthesis of N8-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 Tm, 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 N8-glycosylated 8-aza-2-methylhypoxanthine and methylated purines) and G (N8-glycosylated 8-aza-2-methylhypoxanthine). The base pair formed between N8-glycosylated 8-aza-6-thiohypoxanthine and N9-glycosylated 2-methyl-6-thiohypoxanthine (X2:X6) showed, to some extent, an orthogonal interaction. Based on Tm studies, the only potential self-pairing system is formed by the N8-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.