Studies toward DNA sequence recognition by the Janus Wedge format

CARB 8

Larry W. McLaughlin, Meena Meena, and Han Chen. Department of Chemistry, Boston College, Merkert Chemistry Center, 2609 Beacon St, Chestnut Hill, MA 02467
We describe a new approach to nucleic acid targeting of DNA duplexes. In this format, the targeting strand of DNA inserts itself between the two Watson-Crick faces of the duplex to result in a new type of DNA triplex. These triplexes are termed Janus Wedge triplexes after the Roman god Janus. We have prepared two targeting Janus Wedge residues, one for dA-dT base pairs (W1) and one for dG-dC base pairs (W2). In the recognition complex the wedge strand is hydrogen bonded to both Watson-Crick faces of the target base pair.

We describe the syntheses of the necessary monomeric wedge residues as well as 8-mer and 14-mer helix-targeting probes. We will describe gel-shift experiments, protection experiments and fluorescence experiments designed to characterize the strand-invasion process necessary to permit the targeting of duplex DNA by this format.