Chemical and biological characterization of peptidoglycan and lipopeptides/lipoproteins from Gram-positive bacteria

• Applicant: Professor Dr. Ulrich Zähringer
• Subject Area: Immunology
• Term: from 2002 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5357696

Peptidoglycan (PG) constitutes the cell-wall component (murein) in Gram-negative vertebrates. During the first period of funding we could isolate, purify and fully characterize a hexameric pentadecapeptide [(GM5P)3] and Park`s nucleotide from a soluble peptidoglycan (sPG) preparation of Staphylococcus aureus. Both structures were investigated by chemical analysis, ESI-mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. They were found to be completely inactive as TLR2 ligand, thus further supporting our present working hypothesis. This finding was further corroborated by synthetic PG part structures which all showed no TLR2 activity. In the second period of funding we aim to identify the TLR2 specific indcutor molecule associated with PG (or sPG) which may be a lipoprotein (lipopeptide), lipoteichoic acid (LTA), teichoic acid (TA) modified PG or another lipophilic contaminant. Our project aims to clarify the molecular mechanisms of TLR2 and it is conducted especially in order to understand the molecular basis of "pattern recognition".

• DFG Programme: Priority Programmes
• Subproject of: SPP 1110: Innate Immunity