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JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 287, Issue 32, Pages 27014-27019Publisher
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DOI: 10.1074/jbc.R112.346098
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- NIAID NIH HHS [R01 AI022931] Funding Source: Medline
- NIDCR NIH HHS [R01 DE021341] Funding Source: Medline
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theta-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. theta-Defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel beta-strands. Human theta-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 theta-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 theta-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 theta-defensins make them intriguing potential therapeutic agents.
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