RTD-1: a new type of defensin

Abstract

Tang, Y-Q. et al. (1999) A cyclic anti-microbial peptide produced in primate leukocytes by the ligation of two truncated α-defensins. Science 286, 498–502Innate immune mechanisms exist to provide an immediate response to microbial infection. Recent studies have revealed that innate defense mechanisms are remarkably conserved across species and exhibit some degree of specificity. Anti-microbial peptides, of which the defensins are one class, constitute a major component of innate defense, particularly in plants and insects. Vertebrate defensins, which fall into two structural classes α and β, are cationic molecules which act by preferentially disrupting microbial membranes.A recent paper in Science describes the isolation of a novel anti-microbial peptide from rhesus macaque neutrophils and monocytes, termed rhesus theta defensin 1 (RTD-1). The cyclical structure of this peptide, which more closely resembles porcine protegrins, is unique among defensins and confers increased microbicidal activity compared with an acyclic form. The peptide is formed by the ligation of two truncated α-defensin nonapeptides in a head-to-tail manner. The post-translational mechanism which leads to the formation of RTD-1 has not previously been recognized and requires further characterization. Like protegrins, but unlike other defensins, the microbicidal activity of RTD-1 is resistant to increased salt concentration. This feature of RTD-1, which enables it to retain functional activity at the salt concentrations present in blood, makes it an attractive candidate for the development of therapeutic compounds to replace existing antibiotics.