Conversion of helix-turn-helix motif sequence-specific DNA binding proteins into site-specific DNA cleavage agents

Richard H. Ebright, Yon W. Ebright, P. Shannon Pendergrast, Angelo Gunasekera

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

An approach is presented to construct novel, semisynthetic site-specific DNA cleavage agents that have DNA recognition sites longer than those of the type II restriction endonucleases. To demonstrate the approach, a prototype was constructed in which the chelator 1,10-phenanthroline is incorporated at amino acid 10 of the helix-turn-helix motif of the Escherichia coli catabolite gene activator protein: [(N-acetyl-5-amino-1,10-phenanthroline)-Cys178]CAP. The prototype binds to a 22 base pair DNA recognition site with Kobs = 1 × 108 M-1. In the presence of Cu(II) and reducing agent, the prototype cleaves DNA at four adjacent nucleotides on each DNA strand within the DNA recognition site. The DNA cleavage reaction using 40 base pair and 7164 base pair DNA substrates is demonstrated.

Original languageEnglish (US)
Title of host publicationBiomedical Engineering Perspectives
Subtitle of host publicationHealth Care Technologies for the 1990's and Beyond
PublisherPubl by IEEE
Pages1616
Number of pages1
Editionpt 4
ISBN (Print)0879425598
StatePublished - 1990
EventProceedings of the 12th Annual International Conference of the IEEE Engineering in Medicine and Biology Society - Philadelphia, PA, USA
Duration: Nov 1 1990Nov 4 1990

Publication series

NameProceedings of the Annual Conference on Engineering in Medicine and Biology
Numberpt 4
ISSN (Print)0589-1019

Other

OtherProceedings of the 12th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
CityPhiladelphia, PA, USA
Period11/1/9011/4/90

All Science Journal Classification (ASJC) codes

  • Signal Processing
  • Biomedical Engineering
  • Computer Vision and Pattern Recognition
  • Health Informatics

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