| Chapter 1. Background of DNA double and triple helices is included.;Chapter 2. We were interested in investigating the site-specific recognition of T-A base pairs by oligonucleotide-directed triplex formation. Five 2'-deoxyguanosine (G) analogues replaced G in the G•T-A triplet. The analogue 3-deaza-2'-deoxyguanosine was synthesized and incorporated into a 15mer strand that targeted a 25mer duplex. None of the analogues enhanced triplex formation relative to the G•T-A control.;Chapter 3. A chiral, acyclic glycerol-based linker was used in the third strand to provide more flexibility for base-base interactions. The G-C duplex was targeted by the acyclic nucleoside analogue N7-glycosylated guanine (N7aG). Triplex enhancement was seen with five contiguous N7aG vs. noncontiguous. Years later, a direct comparison was made between the flexible backbone and the rigid ribose backbone after synthesizing 7-(2-deoxy-beta-D-erythro-pentofuranosyl)guanine (N7G). These results indicated that increased flexibility disrupted base stacking for triplex formation in this system.;Chapter 4. We changed the binding site of the third strand from the major groove to the disruption of the Watson-Crick base pairs forming a Janus Wedge complex. Four assays performed indicated that an oligonucleotide Janus Wedge complex is capable of being formed and shows excellent stabilization properties. |
