Glycan-decorated HPMA copolymers as high-affinity lectin ligands
| Autor: | Rafał Konefał, Barbora Mikulová, Jana Krejzová, Kristýna Slámová, Lucie Petrásková, Petr Chytil, Ladislav Bumba, Lenka Kotrchová, Vladimír Křen, Josef Cvačka, Pavla Bojarová, Helena Pelantová, Tomáš Etrych |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Glycan
Polymers and Plastics biology Chemistry Stereochemistry Organic Chemistry Lectin Bioengineering 02 engineering and technology Conjugated system 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences Biochemistry Wheat germ agglutinin Epitope 0104 chemical sciences chemistry.chemical_compound biology.protein Methacrylamide Surface plasmon resonance 0210 nano-technology Conjugate |
| Zdroj: | Polym. Chem.. 8:2647-2658 |
| ISSN: | 1759-9962 1759-9954 |
| Popis: | Novel conjugates of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers tethered with chitooligosaccharidic epitopes of varying lengths were shown to be potent ligands of a model lectin, wheat germ agglutinin (WGA). The azide-functionalized oligosaccharidic epitopes were prepared by the action of Tyr470Asn mutant β-N-acetylhexosaminidase from Talaromyces flavus in a single reaction step and were conjugated to HPMA copolymer precursors in a defined pattern and density through Cu+-catalyzed azide–alkyne cycloaddition. The soluble, biocompatible, and structurally flexible synthetic glycopolymers were studied for their binding to WGA in a competitive enzyme-linked lectin assay (ELLA), and the kinetics of interaction were analyzed by surface plasmon resonance (SPR). To the best of our knowledge, this study presents the first HPMA copolymers derivatized with long oligosaccharides that demonstrate high affinity to a lectin target. The binding affinities in the low nanomolar and subnanomolar ranges place the prepared glycopolymers among the best WGA ligands reported to date. This study demonstrates the targeting potential of these glycopolymers for therapeutically relevant lectins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|