Periodic Reporting for period 4 - SWEETOOLS (Smart Biologics: Developing New Tools in Glycobiology)
Reporting period: 2020-08-01 to 2021-07-31
We also moved forward in the second part of the project devoted to construction of glycopeptide libraries. After extensive optimizations, we are now able to produce sophisticated heteroglycopeptide libraries based on the proposed click reaction/deprotection steps. We have successfully performed screening of such libraries toward model protein (Concanavalin A) and initiated a collaboration where we aim at more interesting, cancer-related proteins (Galectins). First hit glycopeptide sequences have been identified and resynthesized and their binding properties were determined. The methodology will be also used to find new siglec ligands and cytokine mimetics and applied to cancer immunotherapy studies. manuscript describing our optimization study and application of the methodology toward selective galectin 3 inhibitors is under preparation.
To study glycoconjugates from a different perspective, we succeeded in the synthesis and metabolic incorporation of a new sugar derivative. In combination with the developed fluorogenic bioorthogonal reactions (published in due course), we were able to visualize and inspect glycoconjugates on live cells. In addition, the new derivative in combination with other known and complementary metabolic labeling strategies will enable us to perform studies devoted to identification of e.g. sugar-protein, protein-protein interactions in a cellular context. These experiments will deliver important insight into this type of cellular events at the molecular level.
Most importantly, a patent application on the methodology was submitted to European Patent Office. We believe that the methodology has significant translation potential as it enables selective and highly efficient modification of cell surfaces with different moieties. In contrast to genetically modified cells, the methodology enables attachment of non-encodable moieties to cell surfaces, which could significantly broaden the application potential. The resulting cell-surface modified cells can be used in bioimaging, for the construction of smart biomaterials, in regenerative medicine, as drug delivery systems, in immunotherapy and other biomedical applications.
Overall, the project delivered extremely valuable experience to the group and many projects will be further elaborated in the group. The main results were summarized in 8 publications in respected, international journals with several other publications being under preparation. The results were also presented on several conferences (e.g. The chemical biology society conference) and within invited lectures of the PI. Finally, we were able to develop a new methodology that has tremendous potential for practical use. We are currently exploring different ways of applying the method mainly for therapeutic and diagnostic purposes.