Oligoquinoline foldamers as new antimicrobial compounds
Duration: 4 weeks to 12 months depending on the type of internship (can be adjusted to suit the interest of potential candidates)
Detalhes
BACKGROUND
The WHO has declared antimicrobial resistance (AMR) as one of the major public health problems of the 21st century. To address this challenge, researchers are seeking antimicrobials with new modes of action and less prone to resistance. In this regard, antimicrobial peptides (AMPs) have been heralded as a potential solution to AMR because they affect the microbial cell membrane in a non-specific manner, as opposed to traditional antibiotics. However, their peptidic nature has hampered their use in the clinic. For that reason, peptidomimetics (small molecules that mimic the AMPs physicochemical properties and biological activity) have received considerable attention. In this project we seek to explore the antimicrobial potential of quinoline-derived foldamers, i.e. folding oligomers containing quinoline units. Their rigid backbone and preference to adopt helical conformations make them interesting candidates for the development of new proteolytically-stable mimics of -helical amphipathic AMPs with improved antimicrobial activities.
OBJECTIVES
The work will consist in the synthesis of amphipathic foldamers by microwave-assisted solid-phase synthesis; in evaluating the antimicrobial performances/potential of the foldamers against bacteria and fungi; assessment of disruption to key microbial cell structures by fluorescence microscopy and evaluation of foldamer hemolytic activity and cytotoxicity in two major epithelial barrier cell lines.