Research team

Expertise

My research activities fall under spectroscopy and medicinal chemistry. The former include spectroscopic measurements and computational analysis of infrared, Raman, UV-vis absorption, and their chiral variants vibrational circular dichroism, Raman optical activity and electronic circular dichroism. The main application in which I work is conformational analysis of small molecules, absolute configuration determination and analysis of macromolecular structures. Within medicinal chemistry, my expertise revolves around the implementation of pharmacophore scores/representations as the basis for a generative model (ML based), aimed at hit-to-lead or lead optimization.

Exploring the three-dimensional structure of antimicrobial peptides through optical activity spectroscopy. 01/10/2019 - 30/09/2023

Abstract

The rise in antimicrobial resistance (AMR) may lead to international unrest, as it threatens the global society and economics of the future due to the lack of new antibiotics. Therefore, pharmaceutical companies search for novel antibiotics that will neutralize the threat of bacteria exhibiting AMR. Presently, the target of this search is increasingly focused on the promising class of nature-discovered antimicrobial peptides (AMPs). In order to exploit the naturally occurring AMPs in the development of new resistance-free human antibiotics, the activity of these must be related to their mechanism of action. In order to study the three-dimensional structure of AMPs in solution -which provides crucial information regarding the mechanism of action-, chemists traditionally use nuclear magnetic resonance (NMR) spectroscopy. However, when NMR is employed in combination with optical spectroscopic techniques, a more detailed structural picture of the compound becomes available, essential for rational drug design of new antibiotics. This research project aims to combine Raman optical activity, vibrational circular dichroism and electronic circular dichroism with NMR data available in the literature to study AMPs. The AMPs vancomycin, ramoplanin and daptomycin will be subjected to a full structural study, both alone in solution and in interaction with their biological targets within the bacterial cell. The main focus lays on the relationship between the observed spectral features and three-dimensional structural aspects of the compounds. Finally, this will allow for the development of a methodology applicable onto a broad range of AMPs that are of interest in the pharmaceutical world.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project