Retrocyclins: Using past as prologue

    Authors

    A. M. Cole; W. Wang; A. J. Waring;R. I. Lehrer

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Curr. Protein Pept. Sci.

    Keywords

    antiviral; cyclic peptides; HIV-1 uptake inhibitors; lectin; retrocyclin; theta-defensin; HIGH-MANNOSE OLIGOSACCHARIDES; NATURAL PEPTIDE ANTIBIOTICS; PROTEIN; CYANOVIRIN-N; ANTIMICROBIAL PEPTIDES; BETA-DEFENSIN; THETA-DEFENSIN; ORAL MUCOSITIS; LIPID BILAYERS; 2 STATES; HIV-1; Biochemistry & Molecular Biology

    Abstract

    Retrocyclins are synthetic theta-defensins that were reconstructed from genetic blueprints that had remained unused for at least 7.5 million years. From phylogenetic studies, it appears that theta-defensins arose in Old World Monkeys, after that lineage had separated from the prosimians and New World Monkeys. Although some nonhuman primates continue to produce theta-defensin peptides today, Homo sapiens and his gorilla, bonobo, and chimpanzee relatives do not. Their inability to do so reflects the common inheritance of defective theta-defensin genes which contain a premature stop codon that aborts translation. We can only speculate if this ancient genetic event has any contemporary relevance. However, it is noteworthy that synthetic retrocyclins can prevent the entry of HIV-1 and other viruses (e.g., HSV-2) into otherwise susceptible human target cells. Our studies suggest that their antiviral properties are intimately linked to an ability to bind carbohydrate epitopes displayed by viral and cell-surface glycoproteins involved in viral entry. The ability of retrocyclins to recognize and bind carbohydrate and glycan moieties is shared by theta-defensins (RTDs) from rhesus monkeys and by several - but not all - human alpha-defensins. In addition to being the only cyclic peptides of animal origin, the lectin-like activity of theta-defensins gives them the added distinction of being the smallest sugar-binding molecules of natural origin identified to date. This unusual combination makes theta-defensins intriguing molecular prototypes that could be used to design novel carbohydrate-binding or antiviral agents.

    Journal Title

    Current Protein & Peptide Science

    Volume

    5

    Issue/Number

    5

    Publication Date

    1-1-2004

    Document Type

    Review

    Language

    English

    First Page

    373

    Last Page

    381

    WOS Identifier

    WOS:000223753700008

    ISSN

    1389-2037

    Share

    COinS