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α-Diaminobutyric acid-linked hairpin polyamides

Farkas, Michelle E. and Tsai, Sherry M. and Dervan, Peter B. (2007) α-Diaminobutyric acid-linked hairpin polyamides. Bioorganic and Medicinal Chemistry, 15 (22). pp. 6927-6936. ISSN 0968-0896. PMCID PMC2140246. doi:10.1016/j.bmc.2007.07.019. https://resolver.caltech.edu/CaltechAUTHORS:20160509-104247130

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Abstract

A hairpin polyamide-chlorambucil conjugate linked by α-diaminobutyric acid (α-DABA) has been shown to have interesting biological properties in cellular and small animal models. Remarkably, this new class of hairpin polyamides has not been previously characterized with regard to energetics and sequence specificity. Herein we present a series of pyrrole-imidazole hairpin polyamides linked by α-DABA and compare them to polyamides containing the standard γ-DABA turn unit. The α-DABA hairpins have overall decreased binding affinities. However, α-DABA polyamide-chlorambucil conjugates are sequence-specific DNA alkylators with increased specificities. Affinity cleavage studies of α-DABA polyamide-EDTA conjugates confirmed their preference for binding DNA in a forward hairpin conformation. In contrast, an unsubstituted glycine-linked polyamide prefers to bind in an extended binding mode. Thus, substitution on the turn unit locks the α-DABA polyamide into the forward hairpin binding motif.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.bmc.2007.07.019DOIArticle
http://www.sciencedirect.com/science/article/pii/S0968089607006827PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2140246/PubMed CentralArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Alternate Title:Alpha-diaminobutyric acid-linked hairpin polyamides
Additional Information:© 2007 Elsevier. Received 21 June 2007; revised 20 July 2007; accepted 31 July 2007. Available online 22 August 2007. The authors thank the National Institutes of Health for research support and for a predoctoral NRSA training grant to M.E.F. Mass spectrometry analyses were performed in the Mass Spectrometry Laboratory of the Division of Chemistry and Chemical Engineering at the California Institute of Technology.
Funders:
Funding AgencyGrant Number
NIH Predoctoral FellowshipUNSPECIFIED
Issue or Number:22
PubMed Central ID:PMC2140246
DOI:10.1016/j.bmc.2007.07.019
Record Number:CaltechAUTHORS:20160509-104247130
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160509-104247130
Official Citation:Michelle E. Farkas, Sherry M. Tsai, Peter B. Dervan, α-Diaminobutyric acid-linked hairpin polyamides, Bioorganic & Medicinal Chemistry, Volume 15, Issue 22, 15 November 2007, Pages 6927-6936, ISSN 0968-0896, http://dx.doi.org/10.1016/j.bmc.2007.07.019. (http://www.sciencedirect.com/science/article/pii/S0968089607006827)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66744
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:17 May 2016 20:47
Last Modified:11 Nov 2021 00:02

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