Stable peptide inhibitors prevent binding of lethal and oedema factors to protective antigen and neutralize anthrax toxin in vivo

Biochem J. 2006 Apr 1;395(1):157-63. doi: 10.1042/BJ20051747.

Abstract

The lethal and oedema toxins produced by Bacillus anthracis, the aetiological agent of anthrax, are made by association of protective antigen with lethal and oedema factors and play a major role in the pathogenesis of anthrax. In the present paper, we describe the production of peptide-based specific inhibitors in branched form which inhibit the interaction of protective antigen with lethal and oedema factors and neutralize anthrax toxins in vitro and in vivo. Anti-protective antigen peptides were selected from a phage library by competitive panning with lethal factor. Selected 12-mer peptides were synthesized in tetra-branched form and were systematically modified to obtain peptides with higher affinity and inhibitory efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial / metabolism*
  • Bacterial Toxins / antagonists & inhibitors*
  • Bacterial Toxins / metabolism*
  • Cell Death / drug effects
  • Cyclic AMP / metabolism
  • Humans
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Oligopeptides / biosynthesis
  • Peptide Library
  • Peptides / pharmacology*
  • Protein Binding / drug effects
  • Rats
  • Rats, Inbred F344
  • Viper Venoms / antagonists & inhibitors*
  • Viper Venoms / metabolism*

Substances

  • Antigens, Bacterial
  • Bacterial Toxins
  • Oligopeptides
  • Peptide Library
  • Peptides
  • Viper Venoms
  • anthrax toxin
  • edema factor
  • Cyclic AMP