HELICAL ANTIBIOTICS · New Approaches for the recognition of membrane Bilayers - Therapeutic applications

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Project objective

The rapid emergence of bacterial infections resistant to antibiotic drugs has motivated interest in the development of new methods of treatment. In natural systems, antibiotic peptides are part of the first line immunological defence against bacterial infection. These peptides, often having an amphipathic helical structure are believed to exert their effect by the selective disruption of bacterial cell membranes. As this mode of action is not conducive to the development of resistance, they have generated great interest as potential therapeutics. While peptides often have properties such as immunogenicity and instability in vivo that do not favour their development as drugs, it should be possible to design structural analogues with more desirable properties, while maintaining similar or higher activity than the natural peptide antibiotics.The team of Ivan Huc at the European Institute of Chemistry and Biology (IECB) has prepared aromatic oligoamides that fold to form very stable helices in solution. These molecules are versatile scaffolds that are easily prepared synthetically and are expected to be very stable to chemical and biological conditions. Therefore, the goal of this project is to design and synthesize membrane-active antibacterial analogues of these molecules and to study their interactions with membranes using a variety of chemical and biological techniques including NMR, molecular imaging, molecular modelling, phospholipid vesicle models, and bacterial cell culture.These studies will be carried out through collaborations between the Huc group and other teams at the IECB. The results of the project are expected to increase our fundamental understanding of the interaction of amphipathic helices with membranes and to aid in the development of a new class of antimicrobial therapeutics. Furthermore, this project will facilitate the initiation of long-term international collaborations between the researcher and several groups at the IECB.

Original text from CORDIS.

Participants

• UNIVERSITé BORDEAUX 1 · TALENCECoordinatorCity levelFrance

Links

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