Triple helix formation at distant sites

Hybrid oligonucleotides containing a polymeric linker

Donald J. Kessler, Bernard Pettitt, Yuen Kit Cheng, Sean R. Smith, Krishna Jayaraman, Huynh M. Vu, Michael E. Hogan

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

An oligonucleotide hybrid is described which possesses two triple helix forming oligonucleotides which have been connected by a flexible polymeric linker chain. As a prototype, binding of this class of oligonucleotide to duplex DNA has been studied using a segment of the HSV-1 D-glycoprotein promoter, which possesses a pair of 12bp target sites for stable triple helix formation, separated by a duplex spacer region which is one helical turn long. Band shift and footprinting analysis show that such hybrids can bind to both 12bp elements simultaneously, if flexible linkers are included which are longer than 20-25 rotatable bonds. Molecular modeling confirms that a flexible polymeric linker as short as 22 rotatable bonds is enough to link the two distant segments of triple helix, providing that the linker element travels a path which is external to the helix grooves and parallel to the long helix axis.

Original languageEnglish (US)
Pages (from-to)4810-4815
Number of pages6
JournalNucleic Acids Research
Volume21
Issue number20
StatePublished - Oct 11 1993
Externally publishedYes

Fingerprint

Oligonucleotides
Helix
Glycoproteins
Molecular modeling
Human Herpesvirus 1
DNA
Molecular Modeling
Glycoprotein
Promoter
Triple helix
Prototype
Path
Target

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)

Cite this

Kessler, D. J., Pettitt, B., Cheng, Y. K., Smith, S. R., Jayaraman, K., Vu, H. M., & Hogan, M. E. (1993). Triple helix formation at distant sites: Hybrid oligonucleotides containing a polymeric linker. Nucleic Acids Research, 21(20), 4810-4815.

Triple helix formation at distant sites : Hybrid oligonucleotides containing a polymeric linker. / Kessler, Donald J.; Pettitt, Bernard; Cheng, Yuen Kit; Smith, Sean R.; Jayaraman, Krishna; Vu, Huynh M.; Hogan, Michael E.

In: Nucleic Acids Research, Vol. 21, No. 20, 11.10.1993, p. 4810-4815.

Research output: Contribution to journalArticle

Kessler, DJ, Pettitt, B, Cheng, YK, Smith, SR, Jayaraman, K, Vu, HM & Hogan, ME 1993, 'Triple helix formation at distant sites: Hybrid oligonucleotides containing a polymeric linker', Nucleic Acids Research, vol. 21, no. 20, pp. 4810-4815.
Kessler DJ, Pettitt B, Cheng YK, Smith SR, Jayaraman K, Vu HM et al. Triple helix formation at distant sites: Hybrid oligonucleotides containing a polymeric linker. Nucleic Acids Research. 1993 Oct 11;21(20):4810-4815.
Kessler, Donald J. ; Pettitt, Bernard ; Cheng, Yuen Kit ; Smith, Sean R. ; Jayaraman, Krishna ; Vu, Huynh M. ; Hogan, Michael E. / Triple helix formation at distant sites : Hybrid oligonucleotides containing a polymeric linker. In: Nucleic Acids Research. 1993 ; Vol. 21, No. 20. pp. 4810-4815.
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