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Published November 15, 2007 | Supplemental Material + Accepted Version
Journal Article Open

α-Diaminobutyric acid-linked hairpin polyamides

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.

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.

Attached Files

Accepted Version - nihms32234.pdf

Supplemental Material - 1-s2.0-S0968089607006827-fx2.jpg

Supplemental Material - 1-s2.0-S0968089607006827-fx3.jpg

Supplemental Material - 1-s2.0-S0968089607006827-fx4.jpg

Supplemental Material - 1-s2.0-S0968089607006827-fx5.jpg

Supplemental Material - mmc1.pdf

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Additional details

Created:
September 22, 2023
Modified:
October 23, 2023