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Retrocyclins 1 and 2 (also called RC-100 and RC-100b) are novel circular peptides discovered by researchers at UCLA. Retrocyclin 1 and especially retrocyclin 2 show impressive activity against three different viral pathogens: human immunodeficiency virus (HIV-1), herpes simplex virus-1 and herpes simplex virus-2 (HSV-2). Retrocyclin-2 shows activity against a wide library of primary HIV-1 isolates of diverse subtypes, including subtypes A, B, C, CRF01, D, G, and recombinant subtypes. Its effectiveness is not dependent on or restricted by co-receptor (R5, X4 or R5X4) usage. Retrocyclins-1 and 2 may provide valuable platforms to develop analogs with improved pharmacotherapeutic properties. The retrocyclins’ effectiveness against HIV-1 results from the prevention of viral entry, and is correlated to their ability to bind CD4 and gp120 with high affinity. Surface plasmon resonance experiments revealed that retrocyclin-2's affinity (Kd) for gp120 was 9.4 nM and that its affinity for CD4 was 6.7 nM. Fluorescence confocal microscopy of T cells treated with fluorescent RC-101 (an active analogue of retrocyclin-1) revealed surface patches wherein retrocyclin and CD4 were co-localized, without evident peptide internalization. Retrocyclin structures are based on nucleotide sequences found in the human genome and/or in mRNA expressed by human bone marrow that are analogous to RTD or Rhesus Theta Defensin genes. Since human theta-defensin genes and retrocyclin bone marrow mRNA contain a premature stop codon in their signal sequence, retrocyclin peptides are probably not produced in humans. |  RC-100 retrocyclin peptide possible applications for retrocyclin peptidesAs topical agents to protect against the acquisition of HIV-1 infection. As topical agents to protect newborns from HSV-2 infection acquired during vaginal deliver. As topical agents to speed the healing of herpes keratitis, corneal ulceration caused by HSV-1. As systemic agents, used alone or in combination (e.g. HAART), to treat established HIV-1 infection. As topical agents to protect against sexually-acquired HSV-2 infections. As topical and systemic agents directed against additional viruses whose entry-related glycoproteins are bound by retrocyclins and their analogues. | |||||||||||||
References/Further Information:A.M.Cole et al., Proc. Natl. Acad. Sci. USA , 99, 1813 (2002)
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Global Peptide E-headlines