Strategy for Designing Selective Lysosomal Acid α-Glucosidase Inhibitors: Binding Orientation and Influence on Selectivity.
ER α-glucosidase II
drug design
glucosidase inhibitor
iminosugars
ligand docking
lysosomal acid α-glucosidase
molecular dynamics
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
19 Jun 2020
19 Jun 2020
Historique:
received:
27
05
2020
revised:
12
06
2020
accepted:
18
06
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
20
2
2021
Statut:
epublish
Résumé
Deoxynojirimycin (DNJ) is the archetypal iminosugar, in which the configuration of the hydroxyl groups in the piperidine ring truly mimic those of d-glucopyranose; DNJ and derivatives have beneficial effects as therapeutic agents, such as anti-diabetic and antiviral agents, and pharmacological chaperones for genetic disorders, because they have been shown to inhibit α-glucosidases from various sources. However, attempts to design a better molecule based solely on structural similarity cannot produce selectivity between α-glucosidases that are localized in multiple organs and tissues, because the differences of each sugar-recognition site are very subtle. In this study, we provide the first example of a design strategy for selective lysosomal acid α-glucosidase (GAA) inhibitors focusing on the alkyl chain storage site. Our design of α-1-
Identifiants
pubmed: 32575625
pii: molecules25122843
doi: 10.3390/molecules25122843
pmc: PMC7357040
pii:
doi:
Substances chimiques
Antiviral Agents
0
Glycoside Hydrolase Inhibitors
0
Imino Sugars
0
deoxynojirimycine
0
1-Deoxynojirimycin
19130-96-2
alpha-Glucosidases
EC 3.2.1.20
Glucosamine
N08U5BOQ1K
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japanese Society for the Promotion of Science
ID : JSPS KAKENHI Grant Number JP17K08362
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