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Discovery and Characterization of a Disulfide-Locked C2-Symmetric Defensin Peptide

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2014

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American Chemical Society
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Wommack, Andrew J., Joshua J. Ziarek, Jill Tomaras, Haritha R. Chileveru, Yunfei Zhang, Gerhard Wagner, and Elizabeth M. Nolan. 2014. “Discovery and Characterization of a Disulfide-Locked C2-Symmetric Defensin Peptide.” Journal of the American Chemical Society 136 (39): 13494-13497. doi:10.1021/ja505957w. http://dx.doi.org/10.1021/ja505957w.

Abstract

We report the discovery of HD5-CD, an unprecedented C2-symmetric β-barrel-like covalent dimer of the cysteine-rich host-defense peptide human defensin 5 (HD5). Dimerization results from intermonomer disulfide exchange between the canonical α-defensin CysII–CysIV (Cys5–Cys20) bonds located at the hydrophobic interface. This disulfide-locked dimeric assembly provides a new element of structural diversity for cysteine-rich peptides as well as increased protease resistance, broad-spectrum antimicrobial activity, and enhanced potency against the opportunistic human pathogen Acinetobacter baumannii.

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