θ-Defensins: cyclic peptides with endless potential.
θ-Defensins, the only cyclic peptides of animal origin, have been isolated from the leukocytes of rhesus macaques and baboons. Their biogenesis is unusual because each peptide is an 18-residue chimera formed by the head-to-tail splicing of nonapeptides derived from two separate precursors. θ-Defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel β-strands. Human θ-defensin genes contain a premature stop codon that prevents effective translation of the needed precursors; consequently, these peptides are not present in human leukocytes. Synthetic θ-defensins with sequences that correspond to those encoded within the human pseudogenes are called retrocyclins. Retrocyclin-1 inhibits the cellular entry of HIV-1, HSV, and influenza A virus. The rhesus θ-defensin RTD-1 protects mice from an experimental severe acute respiratory syndrome coronavirus infection, and retrocyclin-1 protects mice from infection by Bacillus anthracis spores. The small size, unique structure, and multiple host defense activities of θ-defensins make them intriguing potential therapeutic agents.
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1688, USA. rlehrer@mednet.ucla.edu
Robert I
RI
Lehrer
Alex M
AM
Cole
Michael E
ME
Selsted
D023082:Defensins / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology
D023082:Defensins; D010456:Peptides, Cyclic