Discovery and characterization of a disulfide-locked C(2)-symmetric defensin peptide

J Am Chem Soc. 2014 Oct 1;136(39):13494-7. doi: 10.1021/ja505957w. Epub 2014 Sep 23.


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 Cys(II)-Cys(IV) (Cys(5)-Cys(20)) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Dimerization
  • Disulfides / chemistry*
  • Humans
  • Models, Molecular
  • Structure-Activity Relationship
  • alpha-Defensins / chemical synthesis
  • alpha-Defensins / chemistry*
  • alpha-Defensins / metabolism


  • Anti-Bacterial Agents
  • DEFA5 protein, human
  • Disulfides
  • alpha-Defensins