Title

A Θ-Defensin Composed Exclusively Of D-Amino Acids Is Active Against Hiv-1

Keywords

Enantiopeptide; HIV-1; Retrocyclin; Theta-defensin

Abstract

The ability of certain θ-defensins, including retrocyclin-1, to protect human cells from infection by HIV-1 marks them as potentially useful molecules. θ-Defensins composed of L-amino acids are likely to be unstable in environments that contain host and microbial proteases. This study compared the properties of two enantiomeric θ-defensins, retrocyclin-1, and RC-112. Although these peptides have identical sequences, RC-112 is composed exclusively of D-amino acids, whereas retrocyclin-1 contains only L-amino acids. We compared the ability of these peptides to protect JC53-BL human cells from infection by 30 primary HIV-1 isolates. JC53-BL cells are modified HeLa cells that express surface CD4, CXCR4, and CCR5. They also contain reporter cassettes that are driven by the HIV-1 LTR, and express β-galactosidase and luciferase. The HIV-1 isolates varied in co-receptor specificity and included subtypes A, B, C, D, CRF01-AE, and G. RC-112 was several fold more potent than retrocyclin-1 across the entire HIV-1 panel. Although RC-112 bound immobilized gp120 and CD4 with lower affinity than did retrocyclin-1, surface plasmon resonance experiments performed with 1 μg/mL of RC-112 and retrocyclin-1 revealed that both glycoproteins were bound to a similar extent. The superior antiviral performance of RC-112 most likely reflected its resistance to degradation by surface-associated or secreted proteases of the JC53-BL target cells. θ-Defensins composed exclusively of D-amino acids merit consideration as starting points for designing microbicides for topical application to the vagina or rectum.

Publication Date

6-1-2004

Publication Title

Journal of Peptide Research

Volume

63

Issue

6

Number of Pages

469-476

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1111/j.1399-3011.2004.00155.x

Socpus ID

3042640897 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/3042640897

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