A Cyclic Antimicrobial Peptide Produced in Primate Leukocytes by the Ligation of Two Truncated α-Defensins

• DOI: 10.1126/science.286.5439.498
• Publication Date: 2002-07-27T09:45:50Z
• Authors: Yi-Quan Tang; Jun Yuan; George Ösapay; Klara Ösapay; Dat Tran; Christopher J. Mi...; Andre J. Ouellette; Michael E. Selsted
• Keywords: 0303 health sciences; Bacteria; Neutrophils; Protein Conformation; Molecular Sequence Data; Osmolar Concentration; Fungi; Macaca mulatta; Peptides, Cyclic; Monocytes; Anti-Bacterial Agents; 3. Good health; Defensins; 03 medical and health sciences; Anti-Infective Agents; Protein Biosynthesis; Animals; Humans; Leukopoiesis; Amino Acid Sequence; Disulfides; Cloning, Molecular; Oligopeptides

Analysis of rhesus macaque leukocytes disclosed the presence of an 18-residue macrocyclic, tridisulfide antibiotic peptide in granules of neutrophils and monocytes. The peptide, termed rhesus theta defensin-1 (RTD-1), is microbicidal for bacteria and fungi at low micromolar concentrations. Antibacterial activity of the cyclic peptide was threefold greater than that of an open-chain analog, and the cyclic conformation was required for antimicrobial activity in the presence of 150 millimolar sodium chloride. Biosynthesis of RTD-1 involves the head-to-tail ligation of two α-defensin–related nonapeptides, requiring the formation of two new peptide bonds. Thus, host defense cells possess mechanisms for synthesis and granular packaging of macrocyclic antibiotic peptides that are components of the phagocyte antimicrobial armamentarium.