On-Chip Neo-Glycopeptide Synthesis for Multivalent Glycan Presentation
| Autor: | Peter H. Seeberger, Martina Delbianco, Felix F. Loeffler, Jasmin Heidepriem, Alvaro Mallagaray, Robert Wawrzinek, Vittorio Bordoni, Felix F. Fuchsberger, Daniela S. Mattes, Stephan Eickelmann, Marco Mende, Alexandra Tsouka, Christoph Rademacher, Grigori Paris |
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| Rok vydání: | 2020 |
| Předmět: |
Glycan
010402 general chemistry 01 natural sciences Catalysis Polysaccharides Humans Avidity Binding site laserinduced forward transfer microarrays Engineering & allied operations Binding Sites biology Full Paper 010405 organic chemistry Chemistry Organic Chemistry Glycopeptides Lectin General Chemistry Full Papers Microarray Analysis Glycopeptide 0104 chemical sciences Pattern synthesis laser-induced forward transfer click chemistry Click chemistry Biophysics biology.protein lectin ddc:620 DNA microarray 500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften combinatorial chemistry |
| Zdroj: | Chemistry (Weinheim an Der Bergstrasse, Germany) Chemistry – A European Journal Chemistry-a European journal, 26 (44), 9954-9963 |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | Single glycan–protein interactions are often weak, such that glycan binding partners commonly utilize multiple, spatially defined binding sites to enhance binding avidity and specificity. Current array technologies usually neglect defined multivalent display. Laser‐based array synthesis technology allows for flexible and rapid on‐surface synthesis of different peptides. By combining this technique with click chemistry, neo‐glycopeptides were produced directly on a functionalized glass slide in the microarray format. Density and spatial distribution of carbohydrates can be tuned, resulting in well‐defined glycan structures for multivalent display. The two lectins concanavalin A and langerin were probed with different glycans on multivalent scaffolds, revealing strong spacing‐, density‐, and ligand‐dependent binding. In addition, we could also measure the surface dissociation constant. This approach allows for a rapid generation, screening, and optimization of a multitude of multivalent scaffolds for glycan binding. Interactions of proteins with glycans rely on multivalency, where multiple adjacent binding events are involved. To study this glycan density‐dependent binding, a facile technique to synthesize peptide‐based multivalent carbohydrate scaffolds in parallel, directly on‐chip, in the microarray format, was developed. This allows to rapidly generate arrays of multivalent glycan structures, without the need for individual multistep syntheses per compound. |
| Databáze: | OpenAIRE |
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