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Sequence-specific trapping of topoisomerase I by DNA binding polyamide-camptothecin conjugates

Wang, Clay C. C. and Dervan, Peter B. (2001) Sequence-specific trapping of topoisomerase I by DNA binding polyamide-camptothecin conjugates. Journal of the American Chemical Society, 123 (36). pp. 8657-8661. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20160510-082725087

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Abstract

Hairpin pyrrole−imidazole polyamides are synthetic ligands that bind in the minor groove of DNA with affinities and specificities comparable to those of DNA binding proteins. Three polyamide−camptothecin conjugates 1−3 with linkers varying in length between 7, 13, and 18 atoms were synthesized to trap the enzyme Topoisomerase I and induce cleavage at predetermined DNA sites. One of these, polyamide−camptothecin conjugate 3 at nanomolar concentration (50 nM) in the presence of Topo I (37 °C), induces DNA cleavage between three and four base pairs from the polyamide binding site in high yield (77%).


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja010392pDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja010392pPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja010392pPublisherSupporting Information
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2001 American Chemical Society. Received February 13, 2001; Publication Date (Web): August 16, 2001. We are grateful to the National Institutes of Health (GM-27681) for research support and a traineeship award (GM-08501) to C.C.C.W.
Funders:
Funding AgencyGrant Number
NIHGM-27681
NIH Predoctoral FellowshipGM-08501
Issue or Number:36
Record Number:CaltechAUTHORS:20160510-082725087
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-082725087
Official Citation:Sequence-Specific Trapping of Topoisomerase I by DNA Binding Polyamide−Camptothecin Conjugates Clay C. C. Wang and Peter B. Dervan Journal of the American Chemical Society 2001 123 (36), 8657-8661 DOI: 10.1021/ja010392p
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66821
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:18 May 2016 19:00
Last Modified:26 Nov 2019 11:15

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