Title

Retrocyclins: Using past as prologue

Authors

Authors

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

Comments

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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

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