Project: Fluorinations with implications: enhancing the potential of biologically and medicinally interesting molecules through targeted fluorine introduction

2021-06-01 – 2026-05-31

Abstract

The process of developing bioactive compounds into drugs is

notoriously difficult, costing the pharmaceutical industry years and

billions of dollars per drug. The motivation of our research

programme is to develop methodologies to improve and accelerate

such efforts. The application encompasses three projects, all focused

on improving physical properties of bioactive compounds. It is indeed

only a recent but very firm realisation that physical properties are as

important as bioactivity for a given compound to make it as a drug.

One of these, lipophilicity, a measure for the ease with which

molecules enter cells, has proven to be a crucial parameter in drug

development: no matter how bioactive the molecule, if it cannot enter

cells it is unlikely going to cure disease. One project regards

carbohydrates, which are extremely important biomolecules, but have

very undesired physical properties. We aim to investigate

fundamental aspects of the relationship of carbohydrate structure

and lipophilicity and hydrogen bonding (the most important way

molecules interact with proteins) to be able to improve carbohydrate

properties. A second project aims at refining the very interpretation of

lipophilicity, by disentangling the individual contributions of different

forms of a molecule. The third project is focused on the shape of

molecules: we propose a novel way to control how peptide chains

fold. All projects involve “precision fluorination” of molecules aimed at

modifying properties.