Antimicrobial activities of heparin-binding peptides

Eur J Biochem. 2004 Mar;271(6):1219-26. doi: 10.1111/j.1432-1033.2004.04035.x.


Antimicrobial peptides are effector molecules of the innate immune system. We recently showed that the human antimicrobial peptides alpha-defensin and LL-37 bind to glycosaminoglycans (heparin and dermatan sulphate). Here we demonstrate the obverse, i.e. structural motifs associated with heparin affinity (cationicity, amphipaticity, and consensus regions) may confer antimicrobial properties to a given peptide. Thus, heparin-binding peptides derived from laminin isoforms, von Willebrand factor, vitronectin, protein C inhibitor, and fibronectin, exerted antimicrobial activities against Gram-positive and Gram-negative bacteria. Similar results were obtained using heparin-binding peptides derived from complement factor C3 as well as consensus sequences for heparin-binding (Cardin and Weintraub motifs). These sequence motifs, and additional peptides, also killed the fungus Candida albicans. These data will have implications for the search for novel antimicrobial peptides and utilization of heparin-protein interactions should be helpful in the identification and purification of novel antimicrobial peptides from complex biological mixtures. Finally, consensus regions may serve as templates for de novo synthesis of novel antimicrobial molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / metabolism*
  • Anti-Infective Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Complement C3 / chemistry
  • Consensus Sequence
  • Enterococcus faecalis / drug effects
  • Enterococcus faecalis / growth & development
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Heparin / metabolism*
  • Humans
  • Microbial Sensitivity Tests / methods
  • Microscopy, Electron
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Radioligand Assay


  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Complement C3
  • Heparin