Synthetic lipopeptide adjuvants and Toll-like receptor 2—structure–activity relationships

Bacterial lipoproteins and their synthetic analogues (sLP) are strong immune modulators of the early host responses after infection. Synthetic lipopeptides are strong adjuvants for the adaptive immune system. Lipoproteins and lipopeptides induce signalling in immune cells through Toll-like receptor-...

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Veröffentlicht in:Vaccine 2004-06, Vol.22 (19), p.2494-2499
Hauptverfasser: Spohn, Renate, Buwitt-Beckmann, Ute, Brock, Roland, Jung, Günther, Ulmer, Artur J., Wiesmüller, Karl-Heinz
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Sprache:eng
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Zusammenfassung:Bacterial lipoproteins and their synthetic analogues (sLP) are strong immune modulators of the early host responses after infection. Synthetic lipopeptides are strong adjuvants for the adaptive immune system. Lipoproteins and lipopeptides induce signalling in immune cells through Toll-like receptor-TLR2/TLR1 heterodimers. By screening a combinatorial lipohexapeptide amide collection in an in vitro IL-8 induction assay, we systematically evaluated the potential of 19 proteinogenic amino acids in the peptide moiety of Pam 3Cys-lipopeptides to interact with TLR2. New Pam 3Cys-lipopeptides with high activity were obtained. Different fatty acids were introduced to investigate the influence of the acyl moiety. Lipopeptides with modifications in the core structure of the unusual amino acid S-glycerylcysteine were synthesized and tested for IL-8 induction via TLR2.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2003.11.074