Synthesis of oligonucleotides containing the alkali-labile pyrimidopurinone adduct, M(1)G.

Abstract

An improved method for the synthesis of oligodeoxyribonucleotides containing the endogenous adduct, pyrimido[1,2-a]purin-10(3H)-one (M(1)G), is reported. The key features of the methodology include improved synthesis of the deoxynucleoside of M(1)G by transribosylation with deoxycytidine catalyzed by nucleoside 2'-deoxyribosyltransferase and the use of commercially available 4-tert-butylphenoxyacetyl protecting groups for normal nucleotides. Facile deprotection and removal of the M(1)G-containing oligomers from the solid support were achieved by treatment with a solution of potassium carbonate in methanol. NMR studies were performed to determine the stability of the oligonucleotides at different pHs.