SYNTHESIS AND POSTSYNTHETIC MODIFICATION OF OLIGODEOXYNUCLEOTIDES CONTAINING 4-THIO-2'-DEOXYURIDINE (D(S4)U)

Protected phosphoramidite 2 was used to incorporate synthetically the non-natural nucleoside 4-thio-2'-deoxyuridine (d(S4)U) at a specified position within oligonucleotide 3. Following DNA synthesis, the thioca rbonyl group of the 4-thio-2'-deoxyuridine of 3 was modified chemosele ctively and quantitatively with thiol-specific reagents to afford olig onucleotides 14, 15, and 16 by S-alkylation or mixed disulfide formati on. This protocol represents a divergent postsynthetic modification me thod for incorporating a wide range of functional groups at any base p osition within a DNA strand, starting from a single oligonucleotide in termediate.