ENGINEERING DNA TOPOLOGY WITH LOCKED NUCLEOSIDES: A STRUCTURAL STUDY

DNA dodecamers modified with nucleotide building blocks based on a bicyclo[3.1.0]hexane system that effectively “locks” the ribose template into an RNA-like or “North” (N) conformation were analyzed by various biophysical techniques including high field nuclear magnetic resonance (NMR). Replacement of either one or both of the center thymidines in the Dickerson Drew dodecamer (CGCGAAT*T*CGCG) caused a progressive shift in the bending propensity of the double helix as shown by a newly developed rapid technique that compares the residual dipolar coupling (RDC) values of the modified duplexes with those previously determined for the native DNA.