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Recognition of DNA by designed ligands at subnanomolar concentrations

Trauger, John W. and Baird, Eldon E. and Dervan, Peter B. (1996) Recognition of DNA by designed ligands at subnanomolar concentrations. Nature, 382 (6591). pp. 559-561. ISSN 0028-0836. doi:10.1038/382559a0.

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SMALL molecules that specifically bind with high affinity to any predetermined DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to control rationally the sequence specificity of minor-groove-binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids. Two eight-ring pyrrole–imidazole polyamides differing in sequence by a single amino acid bind specifically to respective six-base-pair target sites which differ in sequence by a single base pair. Binding is observed at subnanomolar concentrations of ligand. The replacement of a single nitrogen atom with a C-H regulates affinity and specificity by two orders of magnitude. The broad range of sequences that can be specifically targeted with pyrrole–imidazole polyamides, coupled with an efficient solid-phase synthesis methodology, identify a powerful class of small molecules for sequence-specific recognition of double-helical DNA.

Item Type:Article
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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1996 Nature Publishing Group. Received 22 March; accepted 25 June 1996. We are grateful to the NIH for research support, to the NSF for a predoctoral fellowship to J.W.T., and to the HHMI for a predoctoral fellowship to E.E.B.
Funding AgencyGrant Number
NSF Predoctoral FellowshipUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:6591
Record Number:CaltechAUTHORS:20150617-085352151
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Official Citation:Recognition of DNA by designed ligands at subnanomolar concentrations 559 John W. Trauger, Eldon E. Baird & Peter B. Dervan doi:10.1038/382559a0
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58306
Deposited By: Ruth Sustaita
Deposited On:17 Jun 2015 16:13
Last Modified:10 Nov 2021 22:02

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