Two-Step Enzymatic Synthesis of beta-D-N-Acetylgalactosamine-(1 -> 4)-D-N-acetylglucosamine (LacdiNAc) Chitooligomers for Deciphering Galectin Binding Behavior

0476013 - MBÚ 2018 RIV DE eng J - Journal Article
Laaf, D. - Bojarová, Pavla - Mikulová, Barbora - Pelantová, Helena - Křen, Vladimír - Elling, L.
Two-Step Enzymatic Synthesis of beta-D-N-Acetylgalactosamine-(1 -> 4)-D-N-acetylglucosamine (LacdiNAc) Chitooligomers for Deciphering Galectin Binding Behavior.
Advanced Synthesis & Catalysis. Roč. 359, č. 12 (2017), s. 2101-2108. ISSN 1615-4150. E-ISSN 1615-4169
R&D Projects: GA ČR GC15-02578J
Institutional support: RVO:61388971
Keywords : chitooligomers * galectin-3 * glycoside hydrolase
OECD category: Biochemistry and molecular biology
Impact factor: 5.123, year: 2017

A two-step synthesis of engineered variants of Talaromyces flavus Beta-N-acetylhexosaminidase (TfHexY470N) and human beta4-galactosyltransferase (beta4GalTY284L) yielded complex glycans comprising a chitooligomeric spacer (beta1,4GlcNAc)n=0-3 terminated with a beta4-linked beta-d-N-acetylgalactosamine-(1-4)-d-N-acetylglucosamine (LacdiNAc) epitope. These compounds are novel inhibitors of human galectin-3 (Gal-3), a widely spread animal lectin with important physiological functions in cellular communication. The multivalent presentation of glycan oligomers was accomplished by chemical conjugation of glycans to lysine residues of bovine serum albumin (BSA). Binding studies of Gal-3 to immobilized BSA neo-glycoconjugates revealed the beneficial influence of the chitooligomeric spacer for the ligand-lectin affinity. We conclude that the use of the (beta1,4GlcNAc)n=0–3 spacer is a perfect nature-like solution for the presentation of elaborated Gal-3 glycan epitopes that surpasses the performance of commonly used synthetic spacers.
Permanent Link: http://hdl.handle.net/11104/0272585