A dimeric form of N-methoxycarbonyl-2-amino-1,8-naphthyridine bound to the A–A mismatch in the CAG/CAG base triad in dsRNA

Abstract

A dimeric form of N-methoxycarbonyl-2-amino-1,8-naphthyridine (MCND) connected at the C2 position with a three-atom linker was examined for the binding to mismatches in double stranded RNA. Despite the fully complementary hydrogen bonding groups to guanine, MCND did not bind to guanine–guanine mismatch but did to adenine–adenine mismatch. The base pairs flanking the mismatch had weak effect on the binding, with showing the strongest binding to the A–A mismatch in the CAG/CAG sequence. The A–A mismatch in the GAC/GAC sequence was a poor substrate for the MCND binding. A monomeric derivative of MCND and another derivative lacking a methylcarbamate group showed negligilble binding to the A–A mismatch and the sequence selectivity. These results are important clues for the better molecular design of RNA binding small molecules.