A theta-defensin composed exclusively of D-amino acids is active against HIV-1.

Abstract

The ability of certain theta-defensins, including retrocyclin-1, to protect human cells from infection by HIV-1 marks them as potentially useful molecules. Theta-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 theta-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 beta-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 microg/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. Theta-defensins composed exclusively of D-amino acids merit consideration as starting points for designing microbicides for topical application to the vagina or rectum.

• Authors: S M Owen, D Rudolph, W Wang, A M Cole, M A Sherman, A J Waring, R I Lehrer, R B Lal
• Journal: The journal of peptide research : official journal of the American Peptide Society (J Pept Res) Vol. 63 Issue 6 Pg. 469-76 (Jun 2004) ISSN: 1397-002X [Print] Denmark
• PMID: 15175019 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amino Acids
• Anti-HIV Agents
• Defensins
• theta-defensin

Topics

• Amino Acids (chemistry)
• Animals
• Anti-HIV Agents (pharmacology)
• Defensins (chemistry, metabolism, pharmacology)
• HIV Infections (drug therapy)
• HIV-1 (drug effects)
• Humans
• Stereoisomerism