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

• Published in: Science (American Association for the Advancement of Science) 1999-10, Vol.286 (5439), p.498-502
• Main Authors: Tang, Yi-Quan, Yuan, Jun, Ösapay, George, Ösapay, Klara, Tran, Dat, Miller, Christopher J., Ouellette, Andre J., Selsted, Michael E.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Analysis of the immune response. Humoral and cellular immunity; Animals; Anti-Bacterial Agents; Anti-Infective Agents - chemistry; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacology; Antibacterials; Antimicrobials; Antiserum; Bacteria - drug effects; Bacteriology; Biological and medical sciences; Bone marrow cells; Cloning, Molecular; Complementary DNA; Defensins; Disulfides; Disulfides - chemistry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Fungi - drug effects; Humans; Immunobiology; Leukocytes; Leukopoiesis; Ligation; Literary Devices; Macaca mulatta; Microbiology; Molecular Sequence Data; Monkeys & apes; Monocytes - metabolism; Neutrophils; Neutrophils - metabolism; Oligopeptides - chemistry; Oligopeptides - genetics; Oligopeptides - metabolism; Organs and cells involved in the immune response; Osmolar Concentration; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Peptides; Peptides, Cyclic - biosynthesis; Peptides, Cyclic - chemistry; Peptides, Cyclic - genetics; Peptides, Cyclic - pharmacology; Protein Biosynthesis; Protein Conformation; Protein Precursors - chemistry; Protein Precursors - genetics; Protein Precursors - metabolism; Protein Processing, Post-Translational; Proteins - chemistry; Proteins - genetics; Proteins - pharmacology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.286.5439.498

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.