New Synthetic Polyoxin Analogs for Chitin Synthesis Inhibition
The natural polyoxins are a class of peptidyl nucleoside antibiotics produced by Streptomyces and characterized by their ability to compete with UDP-GlcNAc for active site binding to chitin synthetase (Hori, et al., 1971 and 1974). As chitin synthetase inhibitors they offer the promise of a new source for clinical antifungal agents. Previous reports have demonstrated that the polyoxins are strong inhibitors of chitin synthetase in vitro, effective at µM concentrations against chitin synthetase of C. albicans (Becker, et al., 1983). However, when assayed for toxicity to zoopathogenic fungi such as Candida albicans or Cryptococcus neoformans concentrations in the mM range were required to observe toxic effects (Becker, et al., 1983).
KeywordsActive Ester Cellular Peptidase Active Site Binding Peptide Portion Chitin Synthesis Inhibition
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