Our research is focused on the development of a next generation method for cost-efficient in situ chemical synthesis of complex biomolecules in the microarray format, such as peptides and glycans. This method allows for a flexible and automated synthesis of biomolecules with a high spot density.
Main characteristic of this method is the direct transfer of compounds via laser irradiation from a donor slide, containing minute amounts of compound within a polymer matrix, to a modified acceptor surface. Next, coupling is achieved between the transferred material and the acceptor via covalent bond formation, by melting the polymer matrix. Finally, repetition of this process with varying donor slides generates a combinatorial pattern, containing e.g. amino acids or glycans.
Our current objective is to combine this laser method with the principle of automated glycan assembly [3-5], to establish high-throughput synthesis of glycans and glycopeptides in the microarray format. This should allow the creation of thousands of different glycan variants in parallel. Subsequently, screening of the synthesized molecules on the microarrays can either be achieved by their selective binding of fluorescently labeled antibodies or glycan binding proteins. The discovery of novel specific molecular interactions via detailed binding studies will lead to novel insights in diagnostics, vaccine development, and disease research. [5-7]
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- Paris, G.; Heidepriem, J.; Tsouka, A.; Mende, M.; Eickelmann, S.; Loeffler, F. F. Automated Laser-Assisted Synthesis of Microarrays for Infectious Disease Research. In Microfluidics, BioMEMS, and Medical Microsystems XVII; Gray, B. L., Becker, H., Eds.; SPIE, 2019; Vol. 10875, p 11.
- Seeberger, P. H. The Logic of Automated Glycan Assembly. Acc Chem Res 2015, 48 (5), 1450–1463.
- Pardo-Vargas, A.; Delbianco, M.; Seeberger, P. H. Automated Glycan Assembly as an Enabling Technology. Curr Opin Chem Biol 2018, 46, 48–55. https://doi.org/10.1016/J.CBPA.2018.04.007.
- Naresh, K.; Schumacher, F.; Hahm, H. S.; Seeberger, P. H. Pushing the Limits of Automated Glycan Assembly: Synthesis of a 50mer Polymannoside. Chem Commun 2017, 53 (65), 9085–9088.
- Pieters, R. J. Maximising Multivalency Effects in Protein–carbohydrate Interactions. Org Biomol Chem 2009, 7 (10), 2013. https://doi.org/10.1039/b901828j.
- Mammen, M.; Choi, S.-K.; Whitesides, G. M. Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors. Angew Chemie Int Ed 1998, 37 (20), 2754–2794.