Document Detail


Protein design of an HIV-1 entry inhibitor.
MedLine Citation:
PMID:  11229405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human immunodeficiency virus type-1 (HIV-1) membrane fusion is promoted by the formation of a trimer-of-hairpins structure that brings the amino- and carboxyl-terminal regions of the gp41 envelope glycoprotein ectodomain into close proximity. Peptides derived from the carboxyl-terminal region (called C-peptides) potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To test the converse of this inhibitory strategy, we designed a small protein, denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants and may serve as the basis for a new class of antiviral agents. The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain.
Authors:
M J Root; M S Kay; P S Kim
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  291     ISSN:  0036-8075     ISO Abbreviation:  Science     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-01     Completed Date:  2001-03-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  884-8     Citation Subset:  IM    
Affiliation:
Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. kimadmin@wi.mit.edu
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Anti-HIV Agents* / chemistry,  immunology,  metabolism,  pharmacology
Carrier Proteins / chemistry*,  metabolism,  pharmacology*
Cell Line
Drug Design*
Giant Cells / drug effects
HIV Antibodies / immunology
HIV Envelope Protein gp41 / chemistry,  metabolism*
HIV-1 / drug effects*,  physiology
Humans
Membrane Fusion / drug effects*
Molecular Sequence Data
Neutralization Tests
Peptide Fragments / chemistry,  immunology,  metabolism
Peptides*
Protein Conformation
Protein Folding
Protein Structure, Secondary
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
P01 GM56552/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/5-helix protein, synthetic; 0/Anti-HIV Agents; 0/Carrier Proteins; 0/HIV Antibodies; 0/HIV Envelope Protein gp41; 0/Peptide Fragments; 0/Peptides

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


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