Synthesis of oligonucleotides containing 2'-deoxy-6-thioguanosine at a predetermined site

Abstract

A new approach has been devised for the synthesis of oligonucleotides containing 2'-deoxy-6-thioguanosine [d(s6G)]. The synthesis of oligonucleotides containing d(s6G) requires special protection and deprotection strategies to prevent the thione functionality from undergoing oxidation and hydrolysis. Previous attempted syntheses have neglected to address this problem. By using the cyanoethyl protecting group for the thione and phenoxyacetyl for the exocyclic amino group, it was possible to deprotect oligonucleotides with a mixture of sodium hydroxide and sodium hydrogen sulfide without any significant conversion of d(s6G) to deoxyguanosine. Application of this strategy will allow investigation of the structural as well as biological activity of d(s6G)-containing oligonucleotides.