Altering the Modular Architecture of Galectins Affects its Binding with Synthetic α-Dystroglycan O-Mannosylated Core M1 Glycoconjugates In situ.

The multifunctionality of galectins helps regulate a broad range of fundamental cellular processes via cis-binding and trans-bridging activities and has gained widespread attention with respect to the importance of the natural specificity/selectivity of this lectin family to its glycoconjugate receptors. Combining galectin (Gal)-1, -3, -4, and -9 variant test panels, achieved via rational protein engineering, and a synthetic α-dystroglycan (DG) O-Mannosylated core M1 glycopeptide library, a detailed comparative analysis was performed, utilizing microarray experiments to delineate the design-functionality relationships within this lectin family. Enhancement of prototype Gal-1 and chimera-type Gal-3 cis-binding toward the prepared ligands is possible by transforming these lectins into tandem-repeat type and prototypes, respectively. Furthermore, Gal-1 variants demonstrated improved trans-bridging capabilities between core M1 α-DG glycopeptides and laminins in microarray, suggesting the possible translational applications of these galectin variants in the treatment of some forms of α-dystroglycanopathy. © 2023 Wiley-VCH GmbH.

Citation

Lareno L Villones, Anna-Kristin Ludwig, Seiya Kikuchi, Rika Ochi, Shin-Ichiro Nishimura, Hans-Joachim Gabius, Herbert Kaltner, Hiroshi Hinou. Altering the Modular Architecture of Galectins Affects its Binding with Synthetic α-Dystroglycan O-Mannosylated Core M1 Glycoconjugates In situ. Chembiochem : a European journal of chemical biology. 2023 Jul 17;24(14):e202200783

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PMID: 36892311

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