In this project, a chemoenzymatic synthesis of glycomimetics has been performed. The first approach focused on G2 derivatives these compounds featured azide-containing glycans (GalNAz) to perform click reaction in order to expand the library. The first approach did not yield any potential candidate, therefore we decided to synthesize asymmetrical compounds and also linear compounds. In addition, we included azidofucose moiety to perform the click reaction. Besides, the preparation of the glycan comprised the linker installation, to this end, we developed a new reaction that make the most of the amino group that is hanging on the anomeric carbon. After obtaining the glycan derivatives, they were printed onto the microarray slides, and afterwards the click reaction was performed to obtain the glycomimetics library that was tested against two different MGL lectins, the MGL-extracellular domain (MGL-ECD) and the carbohydrate recognition domain of the MGL (MGL-CRD). Both MGLs were previously tagged with a fluorescent tag. Preliminary results have been disseminated in departmental meetings and also in the European Chemical Biology Symposium, ECBS (May 2021, virtual conference).
In parallel, two computational works were carried out in collaboration with different groups from several Dutch Universities. In one of the projects, molecular dynamics (MD) simulations were applied to a Glycan-Lectin system to evaluate the binding of different glycans. In the second project, the MD simulations assisted in the identification of the molecular components required in the auxin analogs for their binding to TIR1.
