A family of "click" nucleosides for metal-mediated base pairing: unravelling the principles of highly stabilizing metal-mediated base pairs

Abstract

A family of artificial nucleosides has been developed by applying the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. Starting from 2-deoxy-β-D-glycosyl azide as a common precursor, three bidentate nucleosides have been synthesized. The 1,2,3-triazole involved in all three nucleobases is complemented by 1,2,4-triazole (TriTri), pyrazole (TriPyr), or pyridine (TriPy). Molecular structures of two metal complexes indicate that metal-mediated base pairs of TriPyr may not be fully planar. An investigation of DNA oligonucleotide duplexes comprising the new "click" nucleosides showed that they can bind Ag(I) to form metal-mediated base pairs. In particular the mispair formed from TriPy and the previously established imidazole nucleoside is significantly stabilized in the presence of Ag(I). A comparison of different oligonucleotide sequences allowed the determination of general factors involved in the stabilization of nucleic acids duplexes with metal-mediated base pairs.

Keywords: DNA; bioinorganic chemistry; click chemistry; cycloaddition; silver.