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Cell Mol Life Sci. 2011 Jul;68(13):2231-42. doi: 10.1007/s00018-011-0715-5. Epub 2011 May 7.

Retrocyclins and their activity against HIV-1.

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  • 1Department of Molecular Biology and Microbiology, Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL 32816, USA.


Primate theta-defensins are physically distinguished as the only known fully-cyclic peptides of animal origin. Humans do not produce theta-defensin peptides due to a premature stop codon present in the signal sequence of all six theta-defensin pseudogenes. Instead, since the putative coding regions of human theta-defensin pseudogenes have remained remarkably intact, their corresponding peptides, called "retrocyclins", have been recreated using solid-phase synthetic approaches. Retrocyclins exhibit an exceptional therapeutic index both as inhibitors of HIV-1 entry and as bactericidal agents, which makes retrocyclins promising candidates for further development as topical microbicides to prevent sexually transmitted diseases. This review presents the evolution, antiretroviral mechanism of action, and potential clinical applications of retrocyclins to prevent sexual transmission of HIV-1.

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