Dimerisation behaviour and ligand binding of glycopeptide antibiotics in the presence of d-alanyl-d-lactate cell wall analogues

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Project objective

Research objectives and content The phenomenon of antibiotic resistance in pathogenic bacteria is a serious threat to human health. The antibiotic of last resort is the glycopeptid vancomycin. However, a current rise of vancomycin resistant enterococci (VRE) is observed. This is alarming since there is no drug that can effectively treat a VRE infection. Dimerisation of this antibiotic plays an important role in its antibiotic action, which is promoted by binding to cell wall analogues as di-N-Ac-Lys-D-Ala-D-Ala. Furthermore the introduction of a membrane anchor increases the antibiotic activity. Binding between model systems carrying an D-alanyl-D-lactate residue shall be investigated by NMR techniques and UV difference spectroscopy. A comparison with other cell wall analogues with known binding constants will help to optimise lead structures. As a whole the results will provide substantial information about the mode of antibiotic activity. Training content The project will allow to improve the fellow's knowledge about peptide chemistry and NMR-spectroscopic analysis of these compounds. We hope to be able to find ways to overcome the phenomenon of antibiotic resistance by development of new lead structures in antibiotic research. Links with industry Any lead structure would be further developed and merchandised by the European pharmaceutical industry.

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Participants

• University of Cambridge · CambridgeCoordinatorUnited Kingdom

Links

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