A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins

Analysis of rhesus macaque leukocytes disclosed the presence of an 18-resid ue macrocyclic, tridisulfide antibiotic peptide in granules of neutrophils and monocytes. The peptide, termed rhesus theta defensin-1 (RTD-1), is micr obicidal for bacteria and fungi at Low micromolar concentrations. Antibacte rial activity of the cyclic peptide was threefold greater than that of an o pen-chain analog, and the cyclic conformation was required for antimicrobia l activity in the presence of 150 millimolar sodium chloride. Biosynthesis of RTD-1 involves the head-to-tail ligation of two alpha-defensin-related n onapeptides, requiring the formation of two new peptide bonds. Thus, host d efense cells possess mechanisms for synthesis and granular packaging of mac rocyclic antibiotic peptides that are components of the phagocyte antimicro bial armamentarium.