| DNA recognition: design, synthesis and biophysical characteristics of pyrrole(H) based polyamides. | |
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MedLine Citation:
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PMID: 20632976 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-Methyl imidazole (Im) and N-methyl pyrrole (Py)-containing polyamides that can form stacked dimers can be programmed to target specific DNA sequences in the minor groove of DNA and control gene expression. Polyamides are being investigated as potential medicinal agents for treating diseases including cancer. The naturally occurring polyamide distamycin binds as a dimer in the minor groove of DNA and recognizes sequences rich in A/T and T/A base pairs indiscriminately. Synthetic analogs of distamycin that incorporate N-methylimidazole into the heterocyclic core have been shown to bind to G/C rich sequences with a high degree of specificity. The purpose of this study is to investigate the behavior of polyamides containing the 2,5-linked N-methylpyrrole-2-carboxamide or pyrrole(H) [Py(H)] moiety upon binding to DNA. The synthesis and biophysical characteristics of two polyamides PyPyPyPy(H) 2 and ImPyPyPy(H) 3 designed to test the binding preference of a Py/Pyrrole(H) pairing [Py/Py(H)] and a [Im/Py(H)] is described. Studies utilizing circular dichroism, thermal denaturation (ΔT(M)), biosensor-surface plasmon resonance and DNase I footprinting show that an [Im/Py(H), 3] pairing prefers a G/C or C/G pairing whilst a [Py/Py(H), 2] pairing tolerates A/T or T/A base pairs and avoids a G/C base pair. |
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Authors:
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Sameer Chavda; Keith Mulder; Toni Brown; Hilary Mackay; Balaji Babu; Laura Westrate; Amanda Ferguson; Shicai Lin; Konstantinos Kiakos; Joseph P Ramos; Manoj Munde; W David Wilson; John A Hartley; Moses Lee |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Medicinal chemistry (Shāriqah (United Arab Emirates)) Volume: 6 ISSN: 1875-6638 ISO Abbreviation: Med Chem Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-10-14 Completed Date: 2011-05-19 Revised Date: 2012-03-14 |
Medline Journal Info:
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Nlm Unique ID: 101240303 Medline TA: Med Chem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 150-8 Citation Subset: IM |
Affiliation:
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Department of Chemistry and Division of Natural and Applied Sciences, 49423, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AT Rich Sequence Base Composition* Binding Sites Circular Dichroism / methods DNA / chemistry* GC Rich Sequence Imidazoles / chemistry Models, Molecular Molecular Structure Nylons / chemistry* Pyrroles / chemistry* Surface Plasmon Resonance / methods |
| Grant Support | |
ID/Acronym/Agency:
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C2259/A9994//Cancer Research UK |
| Chemical | |
Reg. No./Substance:
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0/Imidazoles; 0/Nylons; 0/Pyrroles; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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