Title

Retrocyclins: Using Past As Prologue

Keywords

Antiviral; Cyclic peptides; HIV-1 uptake inhibitors; Lectin; Retrocyclin; Theta-defensin

Abstract

Retrocyclins are synthetic θ-defensins that were reconstructed from genetic blueprints that had remained unused for at least 7.5 million years. From phylogenetic studies, it appears that θ-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 θ-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 θ-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 θ-defensins (RTDs) from rhesus monkeys and by several - but not all - human α -defensins. In addition to being the only cyclic peptides of animal origin, the lectin-like activity of θ-defensins gives them the added distinction of being the smallest sugar-binding molecules of natural origin identified to date. This unusual combination makes θ -defensins intriguing molecular prototypes that could be used to design novel carbohydrate-binding or antiviral agents. © 2004 Bentham Science Publishers Ltd.

Publication Date

10-1-2004

Publication Title

Current Protein and Peptide Science

Volume

5

Issue

5

Number of Pages

373-381

Document Type

Review

Personal Identifier

scopus

DOI Link

https://doi.org/10.2174/1389203043379657

Socpus ID

4444328473 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/4444328473

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