PMID: 19949750Dec 2, 2009Paper

Examination of anthrax lethal factor inhibition by siderophores, small hydroxamates, and protamine

Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi
Matthew Thomas, Domenic Castignetti

Abstract

Based on their ability to chelate metals, hydroxamate molecules and siderophores have been successfully used as metalloenzyme inhibitors. As the anthrax toxin lethal factor (LF) is a zinc (Zn)-metallopeptidase, an investigation of the ability of some small non-siderophore hydroxamate compounds, 5 hydroxamate-containing siderophores, and 1 catecholate siderophore was undertaken to determine whether these compounds would inhibit LF. In addition, salmon sperm protamine and ethylenediaminetetraacetic acid were investigated. A spectrophotometric assay of LF activity, based on its reaction with the substrate (Ac-gly-tyr-betaala-arg-arg-arg-arg-arg-arg-arg-arg-val-leu-arg-p-nitroanilide), was used to assess the degree of inhibition of LF by the putative inhibitors. Procedures were implemented to avoid iron contamination of the test solutions and non-ferrated siderophores and hydroxamates were used as potential inhibitors. The hydroxamate-containing siderophores displayed limited capacities to inhibit LF, as did the low molecular weight hydroxamate compounds. In contrast, the catecholate siderophore enterobactin and the cationic polyamine salmon sperm protamine demonstrated notable inhibition of LF at concentrations ranging from approx...Continue Reading

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