DESIGN OF ARTIFICIAL SEQUENCE-SPECIFIC DNA BENDING LIGANDS

Proteins that bend DNA are important regulators of biological processe s. Sequence-specific DNA bending ligands have been designed that bind two noncontiguous sites in the major groove and induce a bend in the D NA, An oligonucleotide containing pyrimidine segments separated by a c entral variable linker domain simultaneously binds by triple helix for mation two 15-bp purine tracts separated by 10 hp. Bend angles of 61 d egrees, 50 degrees, and 38 degrees directed towards the minor groove w ere quantitated by phasing analysis for linkers of four, five, and six T residues, respectively. The design and synthesis of nonnatural arch itectural factors may provide a new class of reagents for use in biolo gy and human medicine.