Synthesis of DNA Interstrand Cross-Links Using a Photocaged Nucleobase

Abstract

The missing linking: BCNU is a chemotherapy drug that generates an ethylene bridge between N1 of deoxyguanosine and N3 of deoxycytidine. No synthesis of a DNA containing this moiety has been reported until now. A new strategy uses a photocaged nucleobase that, when released, generates a highly reactive intermediate which cross-links the opposing DNA strand in a manner analogous to BCNU (see scheme, NBOC=ortho-nitrobenzyloxycarbonyl).