| Targeting multi-stranded DNA structures. | |
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MedLine Citation:
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PMID: 10637359 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The design of agents targeted toward a structure-specific molecular recognition of DNA triplexes or tetraplexes ( quadruplexes ) is discussed, where such structures are relevant to antigene-based chemotherapies and the in situ cellular inhibition of telomerase function, respectively. Using principles that stem from the development of earlier synthetic duplex-binding ligands, together with recent findings that probe structure thermodynamic linkages and kinetic features of stability, a rational approach is developed to exploit the distinct molecular templates offered by these high-order nucleic acid biotarget systems. Such analytical techniques can usefully augment conventional drug design methods, particularly where detailed structural information is unavailable or the mode of binding to form a persistent DNA biotarget ligand complex is not established. Examples from the author s laboratory are used to illustrate structure-specific (or structure-preferential) recognition and subsequent stabilization of DNA triplexes using intercalative or groove-mediated binding mechanisms, and the successful targeting of DNA tetraplexes using planar extended-aromatic ligands. In each case, chemical manipulation of the molecule by exploiting either (i) geometric isomers, (ii) redistribution of charged groups and/or H-bond donors/acceptors, or (iii) optimization of intermolecular pi-overlap can be used to improve the affinity or specificity of the underlying DNA drug binding events. |
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Authors:
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T C Jenkins |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Current medicinal chemistry Volume: 7 ISSN: 0929-8673 ISO Abbreviation: Curr. Med. Chem. Publication Date: 2000 Jan |
Date Detail:
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Created Date: 2000-02-17 Completed Date: 2000-02-17 Revised Date: 2007-02-12 |
Medline Journal Info:
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Nlm Unique ID: 9440157 Medline TA: Curr Med Chem Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 99-115 Citation Subset: IM |
Affiliation:
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Yorkshire Cancer Research Laboratory of Drug Design, University Cancer Medicine Unit, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK. t.c.jenkins@brad.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals DNA / chemistry, drug effects*, metabolism Humans Intercalating Agents / pharmacology Ligands |
| Chemical | |
Reg. No./Substance:
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0/Intercalating Agents; 0/Ligands; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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