Second Structural Motif for Recognition of DNA by Oligonucleotide-Directed Triple-Helix Formation

Abstract

Relative orientations of the DNA strands within a purine⋅purine⋅pyrimidine triple helix have been determined by affinity cleaving. A purine-rich oligonucleotide bound in the major groove of double-helical DNA antiparallel to the Watson-Crick purine strand. Binding depended upon the concentration of multivalent cations such as spermine or Mg 2+ , and appeared to be relatively independent of pH. Two models with specific hydrogen-bonding patterns for base triplets (G⋅GC, A⋅AT, and T⋅AT) are proposed to explain the sequence specificity of binding. The two models differ in the conformation about the glycosyl bond (syn or anti) and the location of the phosphate-deoxyribose backbone in the major groove of DNA. This motif broadens the structural frameworks available as a basis for the design of sequence-specific DNA binding molecules.