Document Detail


A theta-defensin composed exclusively of D-amino acids is active against HIV-1.
MedLine Citation:
PMID:  15175019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The journal of peptide research : official journal of the American Peptide Society     Volume:  63     ISSN:  1397-002X     ISO Abbreviation:  J. Pept. Res.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-03     Completed Date:  2005-02-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9707067     Medline TA:  J Pept Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  469-76     Citation Subset:  IM    
Affiliation:
Division of AIDS, STD, and TB Laboratory Research National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Public Health Services, US Department of Health and Human Services, Atlanta, GA 30333, USA. smo2@cdc.gov
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / chemistry
Animals
Anti-HIV Agents / pharmacology
Defensins / chemistry*,  metabolism,  pharmacology*
HIV Infections / drug therapy
HIV-1 / drug effects*
Humans
Stereoisomerism
Grant Support
ID/Acronym/Agency:
AI 056921/AI/NIAID NIH HHS; AI 22839/AI/NIAID NIH HHS; AI 37945/AI/NIAID NIH HHS; AI 52017/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Anti-HIV Agents; 0/Defensins; 0/theta-defensin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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