Antimicrobial characterization of human beta-defensin 3 derivatives

Antimicrob Agents Chemother. 2003 Sep;47(9):2804-9. doi: 10.1128/AAC.47.9.2804-2809.2003.

Abstract

Human beta-defensin 3 (hBD3) is a highly basic 45-amino-acid protein that acts both as an antimicrobial agent and as a chemoattractant molecule. Although the nature of its antimicrobial activity is largely electrostatic, the importance of the molecular structure on this activity is poorly understood. Two isoforms of hBD3 were synthesized: the first with native disulfide linkages and the second with nonnative linkages. In a third synthetic peptide, all cysteine residues were replaced with alpha-aminobutyric acid, creating a completely linear peptide. A series of six small, linear peptides corresponding to regions of hBD3 with net charges ranging from +4 to +8 (at pH 7) and lengths ranging from 9 to 20 amino acids were also synthesized. The linear full-length peptide showed the highest microbicidal activity against Escherichia coli and Staphylococcus aureus, while all three full-length forms showed equal activity against Candida albicans. The linear peptide also showed high activity against Enterococcus faecium and Pseudomonas aeruginosa. Peptides corresponding to the C terminus showed higher activities when tested against E. coli, with the most active peptides being the most basic. However, only the peptide corresponding to the N terminus of hBD3 showed any activity against S. aureus and C. albicans. Further, N-terminal deletion mutants of native hBD3 showed diminished activities against S. aureus. Thus, the antimicrobial properties of hBD3 derivatives are determined by both charge and structure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents
  • Anti-Infective Agents / chemical synthesis
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Bacteria / drug effects*
  • Colony Count, Microbial
  • Fungi / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Structure-Activity Relationship
  • beta-Defensins / chemical synthesis
  • beta-Defensins / chemistry
  • beta-Defensins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • DEFB103A protein, human
  • beta-Defensins