Combinatorial synthesis of a hyaluronan based polysaccharide library for enhanced CD44 binding
Hyaluronan (HA) plays important roles in a wide range of biological events. The principal receptor of HA in the human body is the Cluster of Differentiation 44 (CD44). To enhance the binding between HA and CD44, a new approach was designed to take advantage of the four-component Ugi reaction. By mod...
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Veröffentlicht in: | Carbohydrate polymers 2023-01, Vol.300, p.120255-120255, Article 120255 |
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Sprache: | eng |
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Zusammenfassung: | Hyaluronan (HA) plays important roles in a wide range of biological events. The principal receptor of HA in the human body is the Cluster of Differentiation 44 (CD44). To enhance the binding between HA and CD44, a new approach was designed to take advantage of the four-component Ugi reaction. By modifying the carboxyl group on HA with various amine, aldehyde, and isocyanide moieties through the Ugi reaction, 36 HA like polysaccharides were generated. Two lead compounds were identified with enhanced CD44 binding compared to unmodified HA, which was confirmed by surface plasmon resonance (SPR), cellular studies and an in vivo mouse tumor model. Ski-learn as a machine learning tool was applied to analyze library data and yield predictions with an accuracy over 80 %. In conclusion, modification of HA via the Ugi reaction can be a promising strategy to develop novel binders toward HA receptors such as CD44.
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•A library of hyaluronan derivatives was synthesized through the Ugi reaction.•New hyaluronan derivatives with enhanced CD44 binding were discovered.•Machine learning algorithms were applied to analyze CD44 binding data. |
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ISSN: | 0144-8617 1879-1344 |
DOI: | 10.1016/j.carbpol.2022.120255 |