Document Detail


Peptide sugar mimetics prevent HIV type 1 replication in peripheral blood mononuclear cells in the presence of HIV-positive antiserum.
MedLine Citation:
PMID:  20156098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cells of the immune system express a number of receptors that bind carbohydrate ligands. We questioned whether peptide mimetics of these ligands will activate phagocytic cells and thereby enhance an antiviral response. Short peptide sequences were identified by computational modeling of docking to glycan-specific lectins, selected as receptor analogs, and incorporated into quadravalent structures by peptide synthesis. A peptide with the sequence HPSLK bound to several lectins specific for monosaccharides and to lectins specific for Neu5Ac-Gal-containing complex glycans, whereas a longer sequence, NPSHPLSG, bound only lectins specific for the more complex glycans. In cultures of peripheral blood mononuclear cells (PBMCs) these peptides stimulated phagocytosis of opsonized microspheres. The peptides inhibited replication of HIV-1 in PBMC cultures by 20-80% at concentrations between 1 nM and 1 muM but inhibited replication 100% in the presence of diluted HIV-positive antiserum that alone inhibited replication by 30%. HPSLK caused about 50% loss of viability of cells at 1 mM, a concentration 10(6)-fold higher than an effective inhibitory concentration, but no toxicity was observed with NPSHPLSG. These results demonstrated that peptidomimetics of glycan ligands of cellular receptors are effective in activating phagocytosis, which may be a factor in providing complete inhibition of HIV-1 replication in vitro.
Authors:
Laura L Eggink; Maria Salas; Carl V Hanson; J Kenneth Hoober
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  26     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-16     Completed Date:  2010-04-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  United States    
Other Details:
Languages:  eng     Pagination:  149-60     Citation Subset:  IM; X    
Affiliation:
Susavion Biosciences, Inc., Tempe, AZ 85281, USA.
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / pharmacology*,  toxicity
Biomimetics*
Cell Survival / drug effects
Cells, Cultured
HIV-1 / drug effects*
Humans
Leukocytes, Mononuclear / virology*
Peptides / pharmacology*,  toxicity
Virus Replication / drug effects*
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Peptides

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


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