title: Solution structure of a purine.purine.pyrimidine DNA triplex containing G.GC and T.AT triples.
abstract: BACKGROUND
  Oligonucleotide-directed triple helix formation allows sequence specific recognition of double helical DNA. This powerful approach has been used to inhibit gene transcription in vitro and to mediate single site specific cleavage of a human chromosome.
  
  
  RESULTS
  Using a combined NMR and molecular dynamics approach (including relaxation matrix refinement), we have determined the solution structure of an intramolecular purine.purine.pyrimidine (R.RY) DNA triplex containing guanines and thymines in the third strand to high resolution. Our studies define the G.GC and T.AT base triple pairing alignments in the R.RY triplex and identify the structural discontinuities in the third strand associated with the non-isomorphism of the base triples. The 5'-d(TpG)-3' base steps exhibit a pronounced increase in axial rise and reduction in helical twist, while the reverse is observed, to a lesser extent at 5'-d(GpT)-3' steps. A third groove is formed between the purine-rich third strand and the pyrimidine strand. It is wider and deeper than the other two grooves.
  
  
  CONCLUSIONS
  Our structure of the R.RY DNA triplex will be important in the design of oligonucleotide probes with enhanced specificity and affinity for targeting in the genome. The third groove presents a potential target for binding additional ligands.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York NY 10032.
authors.forename: I
authors.initials: I
authors.lastname: Radhakrishnan
authors.forename: D J
authors.initials: DJ
authors.lastname: Patel
mesh_terms: D000225:Adenine; D001482:Base Composition; D001483:Base Sequence; D003196:Computer Graphics; D003596:Cytosine; D004247:DNA / Q000737:chemistry*; D006147:Guanine; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011687:Purines; D011743:Pyrimidines; D013941:Thymine
chemical_list: D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D011687:Purines; D011743:Pyrimidines; D006147:Guanine; D003596:Cytosine; D004247:DNA; D000225:Adenine; C030986:pyrimidine; D013941:Thymine