Abstract
New analogues (UPam) of triacylated lipopeptide Pam3CysSK4, a popular agonist of Toll-like receptor 2 (TLR2), were designed making use of the cocrystal structure of a TLR2 heterodimer (with TLR1) with Pam3CysSK4. Twenty-two UPam derivatives that feature an N-tetradecylcarbamyl chain to mimic the native N-palmitoyl moiety and various small amino acids residues at the penultimate N-terminal position were prepared via solid-phase synthesis. In vitro evaluation of immunostimulatory properties revealed new potent TLR2 ligands.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / chemical synthesis
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Adjuvants, Immunologic / chemistry*
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Adjuvants, Immunologic / pharmacology
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Carbamates / chemical synthesis
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Carbamates / chemistry*
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Carbamates / pharmacology
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Cell Line
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Crystallography, X-Ray
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Dendritic Cells / drug effects
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Dendritic Cells / physiology
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Humans
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Lipopeptides / chemical synthesis
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Lipopeptides / chemistry*
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Lipopeptides / pharmacology
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Molecular Structure
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Structure-Activity Relationship
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Toll-Like Receptor 1 / chemistry
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Toll-Like Receptor 2 / agonists*
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Toll-Like Receptor 2 / chemistry
Substances
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Adjuvants, Immunologic
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Carbamates
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Lipopeptides
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Pam(3)CSK(4) peptide
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Toll-Like Receptor 1
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Toll-Like Receptor 2