Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/241481
Type: Artigo de periódico
Title: Synthetic 1,2,3-triazole-linked Glycoconjugates Bind With High Affinity To Human Galectin-3
Author: Marchiori
Marcelo Fiori; Pires Souto
Denio Emanuel; Bortot
Leandro Oliveira; Pereira
Joao Francisco; Kubota
Lauro Tatsuo; Cummings
Richard D.; Dias-Baruffi
Marcelo; Carvalho
Ivone; Campo
Vanessa Leiria
Abstract: This work describes the synthesis of the 1,2,3-triazole amino acid-derived-3-O-galactosides 1-6 and the 1,2,3-triazole di-lactose-derived glycoconjugate 7 as potential galectin-3 inhibitors. The target compounds were synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-derived amino acids N-3-ThrOBn, N-3-PheOBn, N-3-N-Boc-TrpOBn, N-3-N-Boc-LysOBn, N-3-O-tBu-AspOBn and N-3-L-TyrOH, and the corresponding alkyne-based sugar 3-O-propynyl-GalOMe, as well as by click chemistry reaction between the azido-lactose and 2-propynyl lactose. Surface plasmon resonance (SPR) assays showed that all synthetic glycoconjugates 1-7 bound to galectin-3 with high affinity, but the highest binders were the amino acids-derived glycoconjugates 2 (K-D 7.96 mu M) and 4 (KD 4.56 mu M), and the divalent lactoside 7 (K-D1 0.15 mu M/K-D2 19 mu M). Molecular modeling results were in agreement with SPR assays, since more stable interactions with galectin-3 were identified for glycoconjugates 2, 4 and 7. Regarding compounds 2 and 4, they established specific cation-pi (Arg144) and ionic (Asp148) interactions, whereas glycoconjugate 7 was capable to bridge two independent galectin-3 CRDs, creating a non-covalent cross-link between two monomers and, thus, reaching a submicromolar affinity towards galectin-3. (C) 2015 Elsevier Ltd. All rights reserved.
Subject: Arginine-arene Interactions
Molecular-dynamics Method
Trypanosoma-cruzi
Water Models
Amino-acids
Inhibitors
Lectin
Efficient
Receptor
Cell
Country: OXFORD
Editor: PERGAMON-ELSEVIER SCIENCE LTD
Rights: embargo
Identifier DOI: 10.1016/j.bmc.2015.04.044
Address: http://www.sciencedirect.com/science/article/pii/S0968089615003521
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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