Tailored Multivalent Neo-Glycoproteins: Synthesis,
Evaluation, and Application of a Library of Galectin-3-Binding Glycan
Ligands
Version 2 2017-10-18, 19:37
Version 1 2017-10-18, 19:34
Posted on 2017-10-18 - 19:37
Galectin-3 (Gal-3),
a member of the β-galactoside-binding
lectin family, is a tumor biomarker and involved in tumor angiogenesis
and metastasis. Gal-3 is therefore considered as a promising target
for early cancer diagnosis and anticancer therapy. We here present
the synthesis of a library of tailored multivalent neo-glycoproteins
and evaluate their Gal-3 binding properties. By the combinatorial
use of glycosyltransferases and chemo-enzymatic reactions, we first
synthesized a set of N-acetyllactosamine (Galβ1,4GlcNAc;
LacNAc type 2)-based oligosaccharides featuring five different terminating
glycosylation epitopes, respectively. Neo-glycosylation of bovine
serum albumin (BSA) was accomplished by dialkyl squarate coupling
to lysine residues resulting in a library of defined multivalent neo-glycoproteins.
Solid-phase binding assays with immobilized neo-glycoproteins revealed
distinct affinity and specificity of the multivalent glycan epitopes
for Gal-3 binding. In particular, neo-glycoproteins decorated with N′,N″-diacetyllactosamine
(GalNAcβ1,4GlcNAc; LacdiNAc) epitopes showed high selectivity
and were demonstrated to capture Gal-3 from human serum with high
affinity. Furthermore, neo-glycoproteins with terminal biotinylated
LacNAc glycan motif could be utilized as Gal-3 detection agents in
a sandwich enzyme-linked immunosorbent assay format. We conclude that,
in contrast to antibody-based capture steps, the presented neo-glycoproteins
are highly useful to detect functionally intact Gal-3 with high selectivity
and avidity. We further gain novel insights into the binding affinity
of Gal-3 using tailored multivalent neo-glycoproteins, which have
the potential for an application in the context of cancer-related
biomedical research.
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Laaf, Dominic; Bojarová, Pavla; Pelantová, Helena; Křen, Vladimír; Elling, Lothar (2017). Tailored Multivalent Neo-Glycoproteins: Synthesis,
Evaluation, and Application of a Library of Galectin-3-Binding Glycan
Ligands. ACS Publications. Collection. https://doi.org/10.1021/acs.bioconjchem.7b00520
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AUTHORS (5)
DL
Dominic Laaf
PB
Pavla Bojarová
HP
Helena Pelantová
VK
Vladimír Křen
LE
Lothar Elling
KEYWORDS
sandwich enzyme-linked immunosorbent assay formataffinityGalectin -3-Binding Glycan Ligands Galectin -3epitopeterminal biotinylated LacNAc glycan motifneo-glycoproteinTailored Multivalent Neo-GlycoproteinsGal -3 detection agentsgain novel insightsBSAGal -3 bindingGal -3 binding propertiesβ- galactoside-binding lectin familyGal -3Solid-phase binding assays