Selectivity of original C-hexopyranosyl calix[4]arene conjugates towards lectins of different origin.

Autor: Kašáková M; Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic., Malinovská L; Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic., Klejch T; Department of Organic Chemistry, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic., Hlaváčková M; Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic., Dvořáková H; Laboratory of NMR Spectroscopy, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic., Fujdiarová E; Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlarska 2, 611 37, Brno, Czech Republic., Rottnerová Z; Laboratory of Mass Spectrometry, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic., Maťátková O; Department of Biotechnology, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic., Lhoták P; Department of Organic Chemistry, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic., Wimmerová M; Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlarska 2, 611 37, Brno, Czech Republic; Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2. 611 37, Brno, Czech Republic. Electronic address: michaw@chemi.muni.cz., Moravcová J; Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28, Prague, Czech Republic.
Jazyk: angličtina
Zdroj: Carbohydrate research [Carbohydr Res] 2018 Nov; Vol. 469, pp. 60-72. Date of Electronic Publication: 2018 Aug 21.
DOI: 10.1016/j.carres.2018.08.012
Abstrakt: As a part of ongoing activities towards the design of ligands against pathogenic lectins, a synthesis of original α-C-galacto/α-C-manno/α-C-fucopyranosyl glycomimetics based on a calix[4]arene scaffold and their binding evaluation is described. The interactions of the glycomimetics with seven lectins of various origins were carried out using agglutination inhibition assays. The 1,3-alternate tetra-C-fucosylated ligand and its derivative having a tertBu group at the upper rim of the calix[4]arene scaffold were the most potent towards the AAL lectin family (RSL, AFL, AAL, AOL) and BC2L-C. As AFL and RSL originate from important human (Aspergillus fumigatus) and plant (Ralstonia solanacearum) pathogens, the inhibition potency of both leading structures was assessed by surface plasmon resonance. With AFL, both structures exhibited an approximately three orders of magnitude increase in affinity compared to the reference l-fucose. The role of tertBu groups as "aglycon-assisted" events was illustrated by NMR. Furthermore, both compounds showed significantly increased ability to inhibit BC2L-C (from human pathogen Burkholderia cenocepacia) cell agglutination and were able to cross-link whole B. cenocepacia cells. Although the ligands failed to significantly inhibit the agglutination activity of LecA and LecB from Pseudomonas aeruginosa, tetra-C-galactosylated calix[4]arene with tertBu groups at the upper rim of the 1,3-alternate conformation inhibited P. aeruginosa biofilm formation efficiently. This systematic and comprehensive study highlights the fact that hydrolytically stable polyvalent C-glycomimetics should be regarded as potent and selective ligands capable of acting as antiadhesive agents.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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