Benzimidazole-galactosides bind selectively to the Galectin-8 N-Terminal domain: Structure-based design and optimisation.
Benzimidazole
Galectin-8N
Molecular dynamics
Quinoline
Selectivity
X-ray crystallography
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 Nov 2021
05 Nov 2021
Historique:
received:
04
02
2021
revised:
13
06
2021
accepted:
19
06
2021
pubmed:
6
7
2021
medline:
13
10
2021
entrez:
5
7
2021
Statut:
ppublish
Résumé
We have obtained the X-ray crystal structure of the galectin-8 N-terminal domain (galectin-8N) with a previously reported quinoline-galactoside ligand at a resolution of 1.6 Å. Based on this X-ray structure, a collection of galactosides derivatised at O3 with triazole, benzimidazole, benzothiazole, and benzoxazole moieties were designed and synthesised. This led to the discovery of a 3-O-(N-methylbenzimidazolylmethyl)-galactoside with a K
Identifiants
pubmed: 34225180
pii: S0223-5234(21)00513-4
doi: 10.1016/j.ejmech.2021.113664
pii:
doi:
Substances chimiques
Benzimidazoles
0
Galactosides
0
Galectins
0
LGALS8 protein, human
0
Ligands
0
Recombinant Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113664Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest F.R.Z. is an employee of, and H.L. and U.J.N. are shareholders in Galecto Biotech AB, a company developing galectin inhibitors. The other authors have no conflicts to declare.