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Hydroxybenzamide/pyrrole pair distinguishes T·A from A·T base pairs in the minor groove of DNA

Ellervik, Ulf and Wang, Clay C. C. and Dervan, Peter B. (2000) Hydroxybenzamide/pyrrole pair distinguishes T·A from A·T base pairs in the minor groove of DNA. Journal of the American Chemical Society, 122 (39). pp. 9354-9360. ISSN 0002-7863. doi:10.1021/ja001692u.

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A new aromatic pair, 2-hydroxy-6-methoxybenzamide/1-methylpyrrole at the terminal position of hairpin polyamides has been designed for distinguishing T·A from A·T base pairs and both from G·C/C·G in the minor groove of DNA. Four eight-ring hairpin polyamides with benzamide (Bz), 2-hydroxybenzamide (Hb-1), 2-hydroxy-6-methylbenzamide (Hb-2), and 2-hydroxy-6-methoxybenzamide (Hb-3) at the N-terminal position were synthesized. The equilibrium association constants (K_a) were determined at four DNA sites which differ at a single common position, 5‘-TNTACA-3‘ (N = T, A, G, C). Quantitative DNase I footprint titration experiments reveal that (Hb-3)PyPyPy-(R)^H2^Nγ-ImPyPyPy-β-Dp (4) bound the sequences 5‘-TTTACA-3‘ and 5‘-TATACA-3‘ with high affinity; K_a = 2.6 × 10^(10) M^(-1) and K_a = 8.4 × 10^9 M^(-1), respectively, a 3-fold specificity for T vs A was found. Importantly, the sequences 5‘-TGTACA-3‘ and 5‘-TCTACA-3‘ are bound with 50 and 200 times lower affinity, revealing an overall specificity of Hb-3/Py of T > A ≫ G > C. These results expand the repertoire of sequences targetable by hairpin polyamides.

Item Type:Article
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URLURL TypeDescription Information
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2000 American Chemical Society. Received May 16, 2000. Publication Date (Web): September 15, 2000. We are grateful to the National Institutes of Health (GM-27681) for research support, the Knut and Alice Wallenberg Foundation for a postdoctoral fellowship to U.E., and the National Institutes of Health for a research traineeship award (GM-08501) to C.C.C.W. We thank G. M. Hathaway for MALDI-TOF mass spectrometry.
Funding AgencyGrant Number
Knut and Alice Wallenberg FoundationUNSPECIFIED
NIH Predoctoral FellowshipGM-08501
Issue or Number:39
Record Number:CaltechAUTHORS:20160510-083432494
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Official Citation:Hydroxybenzamide/Pyrrole Pair Distinguishes T·A from A·T Base Pairs in the Minor Groove of DNA Ulf Ellervik, Clay C. C. Wang, and Peter B. Dervan Journal of the American Chemical Society 2000 122 (39), 9354-9360 DOI: 10.1021/ja001692u
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66832
Deposited By: Victoria Brennan
Deposited On:10 May 2016 16:54
Last Modified:11 Nov 2021 00:03

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