One of the concepts of glucose-sensitive insulin involves the presence of an intramolecular switch that responds to an increase in blood glucose levels. At the same time, the insulin should maintain its activity at its natural target site despite significant chemical modification of the molecule. In order to achieve both goals, not only the groups involved in the switch itself and their mutual arrangement in the molecule must be optimised, but also the linkers through which they are bound to the side chains of the amino acids of the insulin, as well as the determination of these amino acids for the modification. The direct chemical synthesis of insulin analogues appears to be a good tool for the optimisation of molecules for the primary screening of biological activity. As an example, we have synthesised insulin with a switch based on boronic acid and a diol. The molecule is most likely not optimal as it was assembled from existing reagents and only served to demonstrate the possibilities of the synthesis. Nevertheless, we see the formation of a boronic acid ester. Technical details can be found in the attached file.
