Cellular and Molecular Life Sciences

, Volume 68, Issue 13, pp 2231–2242

Retrocyclins and their activity against HIV-1

  • W. Todd Penberthy
  • Soumya Chari
  • Amy L. Cole
  • Alexander M. Cole
Multi-author review

DOI: 10.1007/s00018-011-0715-5

Cite this article as:
Penberthy, W.T., Chari, S., Cole, A.L. et al. Cell. Mol. Life Sci. (2011) 68: 2231. doi:10.1007/s00018-011-0715-5


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.


RetrocyclinDefensinHIV-1Host defense peptideAntimicrobial peptideAntiviralMicrobicide



Host-defense peptide




Rhesus theta-defensin


CXC chemokine receptor 4


CC chemokine 5


Human neutrophil peptide


Reverse transcriptase inhibitor

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • W. Todd Penberthy
    • 1
  • Soumya Chari
    • 1
  • Amy L. Cole
    • 1
  • Alexander M. Cole
    • 1
  1. 1.Department of Molecular Biology and Microbiology, Burnett School of Biomedical SciencesUniversity of Central Florida College of MedicineOrlandoUSA