Thionucleoside disulfides as covalent constraints of DNA conformation

Full details of a new strategy for cross-linking of duplex oligonucreotides are described. A direct base-to-base disulfide bond is formed by oxidation of two appropriately positioned thionucleoside bases. Cross-link formation between 4-thio-2'-deoxyuridine and 6-thio-2'-deoxyinosine is demonstrated in three sequence contexts (3' to 3', 5' to 5', and opposed). Disulfide for mation occurs in high yield in both duplex and hairpin DNA. Molecular model ing and circular dichroism were used to demonstrate minimal distortion of t he constrained B-DNA double helix. (C) 1999 Elsevier Science Ltd. All right s reserved.