1. N-tetradecylcarbamyl lipopeptides as novel agonists for Toll-like receptor 2.
- Author
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Willems MM, Zom GG, Khan S, Meeuwenoord N, Melief CJ, van der Stelt M, Overkleeft HS, Codée JD, van der Marel GA, Ossendorp F, and Filippov DV
- Subjects
- Adjuvants, Immunologic chemical synthesis, Adjuvants, Immunologic pharmacology, Carbamates chemical synthesis, Carbamates pharmacology, Cell Line, Crystallography, X-Ray, Dendritic Cells drug effects, Dendritic Cells physiology, Humans, Lipopeptides chemical synthesis, Lipopeptides pharmacology, Molecular Structure, Structure-Activity Relationship, Toll-Like Receptor 1 chemistry, Toll-Like Receptor 2 chemistry, Adjuvants, Immunologic chemistry, Carbamates chemistry, Lipopeptides chemistry, Toll-Like Receptor 2 agonists
- 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.
- Published
- 2014
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