Solution structure of a purine·purine·pyrimidine DNA triplex containing G·GC and T·AT triples

Ishwar Radhakrishnan, Dinshaw J. Patel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)135-152
Number of pages18
JournalStructure
Volume1
Issue number2
DOIs
StatePublished - Oct 15 1993

Keywords

  • nuclear magnetic resonance spectroscopy
  • purine·purine·pyrimidine DNA triple helix
  • solution structure

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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