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Discrimination of 5'-GGGG-3',5'-GCGC-3', and 5'-GGCC-3' sequences in the minor groove of DNA by eight-ring hairpin polyamides

Swalley, Susanne E. and Baird, Eldon E. and Dervan, Peter B. (1997) Discrimination of 5'-GGGG-3',5'-GCGC-3', and 5'-GGCC-3' sequences in the minor groove of DNA by eight-ring hairpin polyamides. Journal of the American Chemical Society, 119 (30). pp. 6953-6961. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20160510-101434600

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Abstract

Eight-ring hairpin polyamides which differ only by the linear arrangement of pyrrole (Py) and imidazole (Im) amino acids were designed for recognition of six base pair DNA sequences containing four contiguous G,C base pairs. The respective DNA binding properties of three polyamides, ImImPyPy-γ-ImImPyPy-β-Dp, ImPyImPy-γ-ImPyImPy-β-Dp, and ImImImIm-γ-PyPyPyPy-β-Dp, were analyzed by footprinting and affinity cleavage on a DNA fragment containing the respective match sites 5‘-TGGCCA-3‘, 5‘-TGCGCA-3‘, and 5‘-TGGGGA-3‘. Quantitative footprint titrations demonstrate that ImImPyPy-γ-ImImPyPy-β-Dp binds the designed match site 5‘-TGGCCA-3‘ with an equilibrium association constant of Ka = 1 × 1010 M-1 and >250-fold specificity versus the mismatch sequences, 5‘-TGCGCA-3‘ and 5‘-TGGGGA-3‘. The polyamides ImPyImPy-γ-ImPyImPy-β-Dp and ImImImIm-γ-PyPyPyPy-β-Dp recognize their respective 5‘-TGCGCA-3‘ and 5‘-TGGGGA-3‘ match sites with reduced affinity relative to ImImPyPy-γ-ImImPyPy-β-Dp, but again with high specificity with regard to mismatch sites. These results expand the DNA sequence repertoire targeted by pyrrole-imidazole polyamides and identify sequence composition effects which will guide further second-generation polyamide design for DNA recognition.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja971184tDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja971184tPublisherArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1997 American Chemical Society. Received April 14, 1997. Publication Date (Web): July 30, 1997. Abstract published in Advance ACS Abstracts, July 15, 1997. We are grateful to the National Institutes of Health (GM-2768) for research support, the National Institutes of Health for a research traineeship award (GM-08501) to S.E.S., and the Howard Hughes Medical Institute for a predoctoral fellowship to E.E.B. We thank G. M. Hathaway for MALDI-TOF mass spectrometry.
Funders:
Funding AgencyGrant Number
NIHGM-27681
NIH Predoctoral FellowshipGM-08501
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:30
Record Number:CaltechAUTHORS:20160510-101434600
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-101434600
Official Citation:Discrimination of 5‘-GGGG-3‘, 5‘-GCGC-3‘, and 5‘-GGCC-3‘ Sequences in the Minor Groove of DNA by Eight-Ring Hairpin Polyamides Susanne E. Swalley, Eldon E. Baird, and Peter B. Dervan Journal of the American Chemical Society 1997 119 (30), 6953-6961 DOI: 10.1021/ja971184t
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66874
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:18 May 2016 20:49
Last Modified:26 Nov 2019 11:15

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