OLIGONUCLEOTIDE-DIRECTED TRIPLE-HELIX FORMATION

Oligonucleotide-directed triple-helix formation has introduced new areas of investigation, including the specific control of gene expression, the development of site-specific artificial nucleases and new diagnostic procedures. During the past year, new developments in the structural analysis of triple-helical complexes have appeared. NMR and vibrational spectroscopies together with molecular dynamics and energy-minimization calculations have led to a model of triple-helical DNA which is markedly different from that deduced from previous fiber-diffraction data on homopolymers. Replacement of deoxyribose by ribose or its 2'-O-alkyl derivatives in one or several of the three strands has dramatic effects on triplex stability. New backbones and non-natural bases have been designed to improve triple-helix stability and extend the range of recognition sequences for oligonucleotide binding to double-helical DNA. These recent advances raise new possibilities for the development of biochemical and pharmacological applications based on oligonucleotide-directed triple-helix formation.