Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3
Laboratory for Biomaterials, Institute for Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany
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Author to whom correspondence should be addressed.
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These authors contributed equally to this work.
Academic Editor: Hans Vliegenthart
Biomolecules 2015, 5(3), 1671-1696; https://doi.org/10.3390/biom5031671
Received: 28 May 2015
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Revised: 26 June 2015
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Accepted: 10 July 2015
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Published: 24 July 2015
(This article belongs to the Special Issue Challenges in Glycan, Glycoprotein and Proteoglycan Research)
Carbohydrate-lectin interactions are relatively weak. As they play an important role in biological recognition processes, multivalent glycan ligands are designed to enhance binding affinity and inhibitory potency. We here report on novel neo-glycoproteins based on bovine serum albumin as scaffold for multivalent presentation of ligands for galectins. We prepared two kinds of tetrasaccharides (N-acetyllactosamine and N,N-diacetyllactosamine terminated) by multi-step chemo-enzymatic synthesis utilizing recombinant glycosyltransferases. Subsequent conjugation of these glycans to lysine groups of bovine serum albumin via squaric acid diethyl ester yielded a set of 22 different neo-glycoproteins with tuned ligand density. The neo-glycoproteins were analyzed by biochemical and chromatographic methods proving various modification degrees. The neo-glycoproteins were used for binding and inhibition studies with human galectin-3 showing high affinity. Binding strength and inhibition potency are closely related to modification density and show binding enhancement by multivalent ligand presentation. At galectin-3 concentrations comparable to serum levels of cancer patients, we detect the highest avidities. Selectivity of N,N-diacetyllactosamine terminated structures towards galectin-3 in comparison to galectin-1 is demonstrated. Moreover, we also see strong inhibitory potency of our scaffolds towards galectin-3 binding. These novel neo-glycoproteins may therefore serve as selective and strong galectin-3 ligands in cancer related biomedical research.
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Keywords:
neo-glycoproteins; galectin-3; multivalency; LacDiNAc; chemo-enzymatic synthesis
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MDPI and ACS Style
Böcker, S.; Laaf, D.; Elling, L. Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3. Biomolecules 2015, 5, 1671-1696. https://doi.org/10.3390/biom5031671
AMA Style
Böcker S, Laaf D, Elling L. Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3. Biomolecules. 2015; 5(3):1671-1696. https://doi.org/10.3390/biom5031671
Chicago/Turabian StyleBöcker, Sophia, Dominic Laaf, and Lothar Elling. 2015. "Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3" Biomolecules 5, no. 3: 1671-1696. https://doi.org/10.3390/biom5031671
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