title: N-tetradecylcarbamyl lipopeptides as novel agonists for Toll-like receptor 2.
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.
authors.affiliation: Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Marian M J H P
authors.initials: MM
authors.lastname: Willems
authors.forename: Gijs G
authors.initials: GG
authors.lastname: Zom
authors.forename: Selina
authors.initials: S
authors.lastname: Khan
authors.forename: Nico
authors.initials: N
authors.lastname: Meeuwenoord
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Mario
authors.initials: M
authors.lastname: van der Stelt
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.forename: Jeroen D C
authors.initials: JD
authors.lastname: Codée
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Filippov
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D055666:Lipopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D051194:Toll-Like Receptor 1 / Q000737:chemistry; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D002219:Carbamates; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2