A NOVEL PALINDROMIC TRIPLE-STRANDED STRUCTURE FORMED BY HOMOPYRIMIDINE DODECAMER D-CTTCTCCTCTTC AND HOMOPURINE HEXAMER D-GAAGAG

We have carried out NMR and molecular mechanics studies on a complex f ormed when a palindromic homopyrimidine dodecamer (d-CTTCTCCTCTTC) and a homopurine hexamer (d-GAAGAG) are mixed in 1:1 molar ratio in aqueo us solutions. Such studies unequivocally establish that two strands of each oligomer combine to form a triple-stranded DNA structure with a palindromic symmetry and with six T.A:T and six C+.G:C hydrogen-bonded base triads, The two purine strands are placed head to head, with the ir 3' ends facing each other in the center of the structure. One-half of each pyrimidine strand contains protonated and the other half conta ins non-protonated cytosines, The two half segments containing protona ted cytosines are hydrogen bonded to each of the two purine hexamers t hrough Hoogsteen T.A and C+.G base pairing, The segments containing no n-protonated cytosines are involved in Watson-Crick (A:T and G:C) base pairing, This leads to a palindromic tripler with a C2-dyad symmetry with respect to the center of the structure. The complex is less stabl e at neutral pH, but the cytosines involved in Hoogsteen base pairing remain protonated even under these conditions. Molecular mechanics cal culations using NMR constraints have provided a detailed three-dimensi onal structure of the complex, The entire stretches of purine, and the pyrimidine nucleotides have a conformation close to B-DNA.