Chemoselective Ligations and Strategies for Peptide/Protein

In our group, the use of chemoselective ligations is crucial to construct biomolecular assemblies especially to obtain high molecular weight compounds and sophisticated macromolecular compounds comprising peptide, carbohydrate and nucleic acid moieties, the major barrier of these systems being incompatible chemistries.

For this purpose, we developed the oxime ligation that benefits from the high chemoselectivity and reactivity between the aminooxy function and the carbonyl group (J. Org. Chem 2008). We have shown that this reaction is compatible with other ligations inter alia the CuAAC (copper(I)-catalyzed azide alkyne cycloaddition). This strategy allows efficient and rapid syntheses of biomolecular compounds without intervening isolations and protection schemes (Angew. Chem. 2009 ; Angew. Chem. 2011).

In parallel, we develop the synthesis of small protein such as toxin by using the native chemical ligation (NCL) in collaboration with Smartox Biotechnology (Bioorg. Med. Chem. 2019 ; Org. Lett 2022).