Poly-N-Acetyllactosamine Neo-Glycoproteins as Nanomolar Ligands of Human Galectin-3: Binding Kinetics and Modeling

0488926 - MBÚ 2019 RIV CH eng J - Journal Article
Bumba, Ladislav - Laaf, D. - Spiwok, V. - Elling, L. - Křen, Vladimír - Bojarová, Pavla
Poly-N-Acetyllactosamine Neo-Glycoproteins as Nanomolar Ligands of Human Galectin-3: Binding Kinetics and Modeling.
International Journal of Molecular Sciences. Roč. 19, č. 2 (2018), č. článku 372. E-ISSN 1422-0067
R&D Projects: GA MŠMT(CZ) LTC17005; GA MŠMT(CZ) LM2015047; GA MŠMT(CZ) LM2015064; GA ČR GC15-02578J
Institutional support: RVO:61388971
Keywords : carbohydrate * galectin-3 * galectins in diagnosis
OECD category: Biochemistry and molecular biology
Impact factor: 4.183, year: 2018

Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types. Its involvement in tumor development and proliferation makes this lectin a promising target for early cancer diagnosis and anti-cancer therapies. Gal-3 recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of glycoproteins and glycolipids with a high specificity for internal LacNAc epitopes. This study analyzes the mode and kinetics of binding of Gal-3 to a series of multivalent neo-glycoproteins presenting complex poly-LacNAc-based oligosaccharide ligands on a scaffold of bovine serum albumin. These neo-glycoproteins rank among the strongest Gal-3 ligands reported, with K-d reaching sub-nanomolar values as determined by surface plasmon resonance. Significant differences in the binding kinetics were observed within the ligand series, showing the tetrasaccharide capped with N,N-diacetyllactosamine (LacdiNAc) as the strongest ligand of Gal-3 in this study. A molecular model of the Gal-3 carbohydrate recognition domain with docked oligosaccharide ligands is presented that shows the relations in the binding site at the molecular level. The neo-glycoproteins presented herein may be applied for selective recognition of Gal-3 both on the cell surface and in blood serum.
Permanent Link: http://hdl.handle.net/11104/0283439