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Title: Effect of single pyrrole replacement with β-alanine on DNA binding affinity and sequence specificity of hairpin pyrrole/imidazole polyamides targeting 5'-GCGC-3'.
Authors: Han, Yong-Woon  KAKEN_id
Kashiwazaki, Gengo
Morinaga, Hironobu
Matsumoto, Tomoko
Hashiya, Kaori
Bando, Toshikazu  kyouindb  KAKEN_id
Harada, Yoshie  KAKEN_id
Sugiyama, Hiroshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 韓, 龍雲
Keywords: Pyrrole–imidazole polyamide
Sequence specificity
DNA binding small molecule
Issue Date: 1-Sep-2013
Publisher: Elsevier Ltd.
Journal title: Bioorganic & medicinal chemistry
Volume: 21
Issue: 17
Start page: 5436
End page: 5441
Abstract: N-Methylpyrrole (Py)-N-methylimidazole (Im) polyamides are small organic molecules that can recognize predetermined DNA sequences with high sequence specificity. As many eukaryotic promoter regions contain highly GC-rich sequences, it is valuable to synthesize and characterize Py-Im polyamides that recognize GC-rich motifs. In this study, we synthesized four hairpin Py-Im polyamides 1-4, which recognize 5'-GCGC-3' and investigated their binding behavior with surface plasmon resonance assay. Py-Im polyamides 2-4 contain two, one, and one β-alanine units, replacing the Py units of 1, respectively. The binding affinities of 2-4 to the target DNA increased 430, 390, and 610-fold, respectively, over that of 1. The association and dissociation rates of 2 to the target DNA were improved by 11 and 37-fold, respectively, compared with those of 1. Interestingly, the association and dissociation rates of 3 and 4 were higher than those of 2, even though the binding affinities of 2, 3, and 4 to the target DNA were comparable to each other. The binding affinity of 2 to DNA with a 2bp mismatch was reduced by 29-fold, compared with that to the matched DNA. Moreover, the binding affinities of 3 and 4 to the same mismatched DNA were reduced by 270 and 110-fold, respectively, indicating that 3 and 4 have greater specificities than 2 and are suitable as DNA-binding modules for engineered epigenetic regulation.
Rights: © 2013 The Authors. Published by Elsevier Ltd.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1016/j.bmc.2013.06.005
PubMed ID: 23810670
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