The Boons group has also made significant contributions to the development of methods for visualizing glycoconjugates of living cells. In particular, we have demonstrated that derivatives of dibenzylcyclooctyne are ideal for strain promoted cycloadditions with dipoles such as azides that can be introduced into glycoconjugates by enzymatic transformations. We have also introduced new chemical reports such as nitrile oxides and nitrones that make it possible to more efficiently label complex glycans of living cells. Using the new labelling methodology, we have established that Niemann-Pick type C (NPC) disease, which is a fatal genetic disorder, is associated with a previously unrecognized defect in the recycling of glycoproteins. This is paving the way for the development of a new treatment strategy for the NPC disease. To more readily label cell surface glycans with bioorthogonal groups, we have developed an approach, coined selective exoenzymatic labeling, in which recombinant sialyl transferases and sugar nucleotide donors modified by a biorthogonal group are used for cell surface modification.
Sun T, Yu S-H, Zhao P, Meng L, Moremen KW, Wells L, Steet R, Boons GJ.(2016) One-step selective exoenzymatic labeling (SEEL) strategy for the biotinylation and identification of glycoproteins of living cells. J Am Chem Soc 138(36):11575-11582.
Li X, Fang T, Boons GJ (2014) Preparation of well-defined antibody–drug conjugates through glycan remodeling and strain-promoted azide–alkyne cycloadditions. Angew Chem Int Ed 53(28):7179-7182.
Mbua NE, Flanagan-Steet H, Johnson S, Wolfert MA, Boons GJ, Steet R (2013) Abnormal accumulation of sialylated glycoproteins visualized in Niemann-Pick Type C cells using the chemical reporter strategy. Proc Natl Acad Sci USA 110(25):10207-10212.
Ning X, Guo J, Wolfert MA, Boons GJ (2008) Visualizing metabolically labeled glycoconjugates of living cells by copper-free and fast Huisgen cycloadditions. Angew Chem Int Ed 47(12):2253-2255.