The Nonnatural Deoxyribonucleoside D3 Incorporated in an Intramolecular DNA Triplex Binds Sequence Specifically by Intercalation

Abstract

The synthetic deoxyribonucleoside 1-(2-deoxy-Beta-D-ribofuranosyl)-4- (3-benzamido)phenylimidazole (D3) has been shown to specifically recognize both T(dot)A and C(dot) G base pairs when incorporated into the Hoogsteen paired strand of pyrimidine (dot) purine (dot) pyrimidine triplexes. To further investigate the binding of D3, a DNA oligonucleotide containing a single D3 residue and designed to form intramolecular triplexes was synthesized and studied by one- and two-dimensional NMR spectroscopy. The oligonucleotide D(AGATAGAACCCCTTCTATCTTATATCTD3TCTT) was found to form a stable intramolecular triplex, with a CCCC and a TATA loop connecting the Watson-Crick and Hoogsteen paired strands, respectively. Unlike other third strand bases, however, D3 does not hydrogen bond with a Watson-Crick base pair. Instead, it intercalates between its associated base pair (T(dot)A) and the adjacent 3' T(dot)A(dot)T triplet. The binding mode of D3 is unique in that it not only binds by intercalation but skips a potential base pair to do so. Thus, non-purine bases can be accommodated in the purine strand of DNA triplexes in an entirely new way

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1993
Accession Number
ADA265580

Entities

People

  • Juli Feigon
  • Karl M. Koshlap
  • Paul Gillespie
  • Peter B. Dervan

Organizations

  • California Institute of Technology

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  • Biochemistry
  • California
  • Chemical Compounds
  • Chemical Engineering
  • Chemistry
  • Engineering
  • Hydrogen
  • Hydrogen Bonds
  • Military Research
  • Molecular Biology
  • Nucleosides
  • Pyrimidines
  • Sequences
  • Two Dimensional
  • United States
  • United States Government

Fields of Study

  • Chemistry

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  • Molecular Genetics