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On the pairing rules for recognition in the minor groove of DNA by pyrrole-imidazole polyamides

White, Sarah and Baird, Eldon E. and Dervan, Peter B. (1997) On the pairing rules for recognition in the minor groove of DNA by pyrrole-imidazole polyamides. Chemistry and Biology, 4 (8). pp. 569-578. ISSN 1074-5521. doi:10.1016/S1074-5521(97)90243-X.

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Background: Cell-permeable small molecules that target predetermined DNA sequences with high affinity and specificity have the potential to control gene expression. A binary code has been developed to correlate DNA sequence with side-by-side pairings between N-methylpyrrole (Py) and N-methylimidazole (lm) carboxamides in the DNA minor groove. We set out to determine the relative energetics of pairings of Im/Py, Py/Im, Im/Im, and Py/Py for targeting G·C and A·T base pairs. A key specificity issue, which has not been previously addressed, is whether an Im/Im pair is energetically equivalent to an Im/Py pair for targeting G·C base pairs. Results: Equilibrium association constants were determined at two five-base-pair sites for a series of four six-ring hairpin polyamides, in order to test the relative energetics of the four aromatic amino-acid pairings opposite G·C and A·T base pairs in the central position. We observed that a G·C base pair was effectively targeted with Im/Py but not Py/Im, Py/Py, or Im/Im. The A·T base pair was effectively targeted with Py/Py but not Im/Py, Py/Im, or Im/Im. Conclusions: An Im/Im pairing is energetically disfavored for the recognition of both A·T and G·C. This specificity will create important limitations on undesirable slipped motifs that are available for unlinked dimers in the minor groove. Baseline energetic parameters will thus be created which, using the predictability of the current pairing rules for specific molecular recognition of double-helical DNA, will guide further second-generation polyamide design for DNA recognition.

Item Type:Article
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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1997 Current Biology. We are grateful to the National Institutes of Health (Grant GM-27681) for research support, to the National Science Foundation for a predoctoral fellowship to SW., and to the Howard Hughes Medical Institute for a predoctoral fellowship to E.E.B.
Funding AgencyGrant Number
NSF Predoctoral FellowshipUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:binary code, gene regulation, hydrogen bond, molecular recognition
Issue or Number:8
Record Number:CaltechAUTHORS:20160510-102057054
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Official Citation:Sarah White, Eldon E. Baird, Peter B. Dervan, On the pairing rules for recognition in the minor groove of DNA by pyrrole-imidazole polyamides, Chemistry & Biology, Volume 4, Issue 8, August 1997, Pages 569-578, ISSN 1074-5521, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66878
Deposited By: Victoria Brennan
Deposited On:18 May 2016 19:24
Last Modified:11 Nov 2021 00:23

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