Synthetic construction of sugar-amino acid hybrid polymers involving globotriaose or lactose and evaluation of their biological activities against Shiga toxins produced by Escherichia coli O157:H7.

Autor: Matsuoka K; Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan; Medical Innovation Research Unit (MiU), Advanced Institute of Innovative Technology (AIIT), Saitama University, Sakura, Saitama 338-8570, Japan. Electronic address: koji@fms.saitama-u.ac.jp., Nishikawa K; Department of Molecular Life Sciences, Graduate School of Life and Medical Sciences, Doshisha University, 1-3 Miyakotani, Tatara, Kyotanabe, Kyoto 610-0394, Japan., Goshu Y; Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan., Koyama T; Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan., Hatano K; Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan; Medical Innovation Research Unit (MiU), Advanced Institute of Innovative Technology (AIIT), Saitama University, Sakura, Saitama 338-8570, Japan., Matsushita T; Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan; Medical Innovation Research Unit (MiU), Advanced Institute of Innovative Technology (AIIT), Saitama University, Sakura, Saitama 338-8570, Japan., Watanabe-Takahashi M; Department of Molecular Life Sciences, Graduate School of Life and Medical Sciences, Doshisha University, 1-3 Miyakotani, Tatara, Kyotanabe, Kyoto 610-0394, Japan., Natori Y; Department of Health Chemistry, School of Pharmacy, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan., Terunuma D; Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2018 Dec 01; Vol. 26 (22), pp. 5792-5803. Date of Electronic Publication: 2018 Oct 30.
DOI: 10.1016/j.bmc.2018.10.023
Abstrakt: Synthetic assembly of sugar moieties and amino acids in order to create "sugar-amino acid hybrid polymers" was accomplished by means of simple radical polymerization of carbohydrate monomers having an amino acid-modified polymerizable aglycon. Amines derived from globotriaoside and lactoside as glycoepitopes were condensed with known carbobenzyloxy derivatives, including Z-Gly, Z-l-Ala and Z-β-Ala, which had appropriate spacer ability and a chiral center to afford fully protected sugar-amino acid hybrid compounds in good yields. After deprotection followed by acryloylation, the water-soluble glycomonomers were polymerized with or without acrylamide in the presence of a radical initiator in water to give corresponding copolymers and homopolymers, which were shown by SEC analysis to have high molecular weights. Evaluation of the biological activities of the glycopolymers against Shiga toxins (Stxs) was carried out, and the results suggested that glycopolymers having highly clustered globotriaosyl residues had high affinity against Stx2 (K D  = 2.7∼4.0 µM) even though other glycopolymers did not show any affinity or showed very weak binding affinity. When Stx1 was used for the same assay, all of the glycopolymers having globotriaosyl residues showed high affinity (K D  = 0.30∼1.74 µM). Interestingly, couple of glycopolymers having lactosyl moieties had weaker binding affinity against Stx1. In addition, when cytotoxicity assays were carried out for both Stxs, glycopolymers having highly clustered globotriaosyl residues showed higher affinity than that of the copolymers, and only highly clustered-type glycopolymers displayed neutralization potency against Stx2.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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