Synthesis and characterization of disulfide cross-linked oligonucleotides

Abstract

Disulfide cross-linked derivatives of the «Dickerson/Drew dodecamer» 5'-d(CGCGAATTCGCG)-3' and the related decamer 5'-d(GCGAATTCGC)-3' have been synthesized, each bearing a dithiobis(ethane) (C 2 ) or dithiobis(propane) (C 3 ) cross-link at the central adenine (A). NMR and CD spectroscopy indicate that these duplexes are essentially undistorted relative to native B-DNA. However, cross-lining does confer a large degree of stabilization upon the duplexes, as reflected in increased melting temperatures of 15-21 o C for the cross-linked oligonucleotides relative to those for the native sequences. In contrast, un-cross-linked tethers at the same adenines cause substantial decreases in the melting temperature