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Bacterial lipoproteins⁄peptides are composed of di-O-acylated-S-(2,3-dihyd-roxypropyl)-cysteinyl residues N-terminally coupled to distinct polypep-tides, which can be N-acylated with a third fatty acid. Using a synthetic lipopeptide library we characterized the contribution of the lipid portion to the TLR2 dependent pattern recognition. | iFEBS Journal Lipopeptide structure determines TLR2 dependent cell activation level Ute Buwitt-Beckmann1 Holger Heine1 Karl-Heinz Wiesmuller2 Gunther Jung3 Roland Brock4 and Artur J. Ulmer1 1 Department of Immunology and CellBiology Research Center Borstel Borstel Germany 2 EMC microcollections GmbH Tubingen Germany 3 Institute of Organic Chemistry University of Tubingen Tubingen Germany 4 Department of Molecular Biology Institute for Cell Biology University of Tubingen Tubingen Germany Keywords TLR2 lipopeptides ligand recognition structure-activity relationship Correspondence A. J. Ulmer Research Center Borstel Parkallee 22 23845 Borstel Germany Tel 49 4537 188448 Fax 49 4537 188435 E-mail ajulmer@fz-borstel.de Received 19 August 2005 revised 13 October 2005 accepted 20 October 2005 doi 10.1111 j.1742-4658.2005.05029.x Bacterial lipoproteins peptides are composed of di-O-acylated-S- 2 3-dihyd-roxypropyl -cysteinyl residues N-terminally coupled to distinct polypeptides which can be N-acylated with a third fatty acid. Using a synthetic lipopeptide library we characterized the contribution of the lipid portion to the TLR2 dependent pattern recognition. We found that the two ester bound fatty acid length threshold is beyond eight C atoms because almost no response was elicited by cellular challenge with analogues carrying shorter acyl chains in HEK293 cells expressing recombinant human TLR2. In contrast the amide bound fatty acid is of lesser importance. While two ester-bound palmitic acids mediate a high stimulatory activity of the respective analogue a lipopeptide carrying one amide-bound and another ester-bound palmitic acid molecule was inactive. In addition species specific LP recognition through murine and human TLR2 depended on the length of the two ester bound fatty acid chains. In conclusion our results indicate the responsibility of both ester bound acyl chains but not of the amide bound fatty acid molecule for the TLR dependent cellular recognition of .
