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 Mg2+, 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.