During the project, the two major objectives could be reached:
1) New method to functionalize biomolecules, in particular proteins: in a team work with biologists, we were able to develop reagents able to selectively modify a single amino acid residue in proteins. Our "hypervalent iodine reagents" displayed unique reactivity and selectivity, and allow for example to introduce fluorescent molecules into proteins to study the biology of the cell. We can also use these reagents to identify the target of bioactive compounds, such as natural products and drugs, a process essential to develop new medication. Another application we developed in collaboration is the selective modification of antibodies, which opens the way for drug-antibody conjugates, with the potential for cures with less side effects. We were able to use our reagents to stabilize bioactive peptide, demonstrating increased binding affinity towards important targets for cancer therapy. The introduction of hypervalent iodine reagents on peptides enable completely new types of bioorthogonal chemistry. This enabled us to synthesize cyclic peptides using very mild catalytic conditions, either using light-activation or commercially available non-toxic gold catalysts. Promising applications of the synthetized compounds as protein inhibitors or as dyes for cell imaging have already been identified.
2) The selective functionalization of alkynes (carbon carbon triple bonds) using commercially available tethering molecules and a palladium catalyst. This reaction gives access to amino alcohols, essential structural elements, especially for medicinal chemistry. Indeed, more than 300'000 amino alcohols have already been reported. They can be found in more than 2000 natural products and 80 FDA approved drugs. The enantioselective selective synthesis of such essential building blocks is already an important result for the SeleCHEM project. From the fundamental point of view, we introduced a new strategy in asymmetric synthesis: the catalytic generation of chiral auxiliaries. This new method combines the advantages of two classical approaches in the field (chiral auxiliary control and enantioselective catalysis), resulting in the best compromise between efficiency and generality.
Our research has therefore contributed to a more selective chemistry (SeleCHEM) for both the modification of small synthetic compounds and large biomolecules. We have disseminated our results already through 19 peer-reviewed publications, which are easily accessible from our project website, more than 25 presentations in conferences, and social media (twitter (no "X") and Linkedin.
