Synthesis of oligonucleotides containing an O~6-G-alkyl-O~6-G interstrand cross-link

摘要

A methodology to synthesize oligonucleotides containing an alkyl interstrand cross-link between the two O6 atoms of deoxyguanosine has been developed.This cross-link is designed to serve as a stable structural mimic of the lesion formed in duplex DNA with the bifunctional alkylating agent hepsulfam.The O6-alkyl coupling is performed via a Mitsunobu reaction between a nucleoside and mono-protected 1,7-heptanediol.Solid-phase oligonucleotide synthesis using a nucleoside bis-phosphoramidite allows for the assembly of the cross-linked duplex.Sufficient quantities of this cross-linked duplex were obtained for various structural and biological investigations.