Triple helix formation at distant sites: Hybrid oligonucleotides containing a polymeric linker

Donald J. Kessler, B. Montgomery Pettitt, Yuen kit Cheng, Sean R. Smith, Krishna Jayaraman, Huynh M. Muv, Michael E. Hogan

Research output: Contribution to journalArticle

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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
DOIs
StatePublished - Oct 11 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Kessler, D. J., Pettitt, B. M., Cheng, Y. K., Smith, S. R., Jayaraman, K., Muv, 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. https://doi.org/10.1093/nar/21.20.4810