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Science 15 October 1999:
Vol. 286. no. 5439, pp. 498 - 502
DOI: 10.1126/science.286.5439.498
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Research Articles

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

Yi-Quan Tang, 1 Jun Yuan, 1 George Ösapay, 1 Klara Ösapay, 1 Dat Tran, 1 Christopher J. Miller, 2 Andre J. Ouellette, 1 Michael E. Selsted 1*

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 alpha -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.

1 Department of Pathology, College of Medicine, University of California, Irvine, CA 92697, USA.
2 California Regional Primate Research Center and Center for Comparative Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
*   To whom correspondence should be addressed. E-mail: meselste{at}uci.edu

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