Clinical features and genetic analysis of 5 cases of infantile-type glycogen storage disease type II: Case reports DOI Creative Commons
Qi Feng, Meng Zhang,

Chun Xiao Ba

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(35), P. e39534 - e39534

Published: Aug. 30, 2024

Objective: Clinical and genetic mutation analysis was performed on 5 infantile glycogen storage disease type II children in Chinese mainland. Methods: data of with infantile-type due to the acidic α-glucosidase ( GAA ) gene variants diagnosed treated at Hebei Provincial Children’s Hospital from January 2018 April 2020 were retrospectively analyzed. Results: Among cases, 1 female 4 male, age first diagnosis 2 months 7 months. The symptoms all cases showed progressive muscle weakness, hypotonia, motor developmental backwardness, them had abnormally elevated creatine kinase, echocardiograms suggested different degrees myocardial hypertrophy, ejection fractions ranging 44% 67%. Analysis variations: compound heterozygous, a total 12 variant loci detected, which c.2024_2026delACA, c.2853G > A, c.1124G T, c.574G c.2509C c.2013G A new mutations that not been reported. Follow-up: All died before year age, death ranged 11.5 months, mean survival time 9.8 Conclusion: Peripheral blood testing alpha-glucosidase enzyme activity is an effective method for diagnosing this disease.

Language: Английский

A stable GH31 α-glucosidase as a model system for the study of mutations leading to human glycogen storage disease type II DOI Creative Commons
Roberta Iacono, Francesca Maria Pia Paragliola, Andrea Strazzulli

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: Feb. 24, 2025

GH31 glycosidases are widespread across organisms, but remarkably, less than 1% of them have been biochemically characterised to date. Among them, human lysosomal acid α-glucosidase (GAA) stands out due its link Pompe disease, a rare storage disorder caused by deficiency. This disease results in glycogen accumulation, severe cellular damage, motor impairment, and premature death. Structural functional studies GAA mutants challenging their instability lack activity, hindering expression purification. The enzyme MalA from hyperthermophilic archaeon is explored here as stable homolog GAA. highly expressible, easy purify, structurally characterised. R400H mutant MalA, corresponding the pathogenic R600H mutation, revealed 1200-fold drop specificity constant >8 °C reduction thermal stability. We propose MalA's robust model for studying mutations developing therapeutic chaperones.

Language: Английский

Citations

0
Indolyl imine compounds as multi-target agents; synthesis, antidiabetic, anticholinesterase, antioxidant activities and molecular modeling DOI

Sadık M. Ceyhan,

İrem Nur Zengin,

Murat Bingül

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1309, P. 138159 - 138159

Published: March 27, 2024

Language: Английский

Citations

3
In Silico Investigation against Inhibitors of Alpha-Amylase Using Structure-based Screening, Molecular Docking, and Molecular Simulations Studies DOI
Fariya Khan, Altaf Ahmad Shah, Ajay Kumar

et al.

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(3), P. 2873 - 2888

Published: July 9, 2024

Language: Английский

Citations

3
Synthesis, in vitro enzyme kinetics and molecular docking studies of the 2-formylphenyl sulfonates and their hydrazone derivatives as potential anti-diabetic and anti-inflammatory agents DOI Creative Commons

Emmanuel N. Agbo,

Redolf S. Segodi, Njabulo Joyfull Gumede

et al.

Results in Chemistry, Journal Year: 2024, Volume and Issue: 7, P. 101453 - 101453

Published: Jan. 1, 2024

The in vitro anti-diabetes and anti-inflammatory inhibitory activities of the synthesized 2-formylphenyl sulfonates their hydrazone derivatives were evaluated through enzymatic assays as potential α-glucosidase lipoxygenase (LOX-15) inhibitors. preliminary results obtained, revealed that prepared compounds are good inhibitors compared to (LOX-15). Compounds 2 g 3 h found exhibit significant against with IC50 values 3.1 µM 2.6 µM, respectively. Moderate activity was also observed for compound 3a (IC50 = 7.3 µM) this enzyme. Enzyme kinetics studies most active (3 h) suggested a mixed mode inhibition α-glucosidase. molecular docking dynamics simulation g, into sites used predict binding modes structure relationship these compounds. demonstrated is due its ability bind both catalytic secondary

Language: Английский

Citations

2
Synthesis, in vitro and in silico evaluation of indole linked carbohydrazides and 1,3,4-oxadiazoles as new α-glycosidase inhibitors DOI

Kubra Kocaman,

Murat Bingül,

Sadık M. Ceyhan

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1325, P. 141057 - 141057

Published: Dec. 9, 2024

Language: Английский

Citations

2
Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases DOI Creative Commons

Daniël van der Gracht,

R.J. Rowland,

V. Roig-Zamboni

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(34), P. 9136 - 9144

Published: Jan. 1, 2023

Parallel FluoPol-ABPP screenings on lysosomal β-glucosidase (GBA1) and α-glucosidase (GAA) revealed a N -9-phenanthrenyl-DNJ that inhibits GAA selectively is an interesting hit for the development of chaperones Pompe disease.

Language: Английский

Citations

4
GAA/(Au–Au/IrO2)@Cu(PABA) reactor with cascade catalytic activity for α-glucosidase inhibitor screening DOI
Yingying Zhong, Qing Wang, Zijian Chen

et al.

Analytica Chimica Acta, Journal Year: 2024, Volume and Issue: 1298, P. 342408 - 342408

Published: Feb. 23, 2024

Language: Английский

Citations

1
Epi-Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses DOI Creative Commons
Melissa Thaler, Tim P. Ofman, Ken Kok

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(8), P. 1594 - 1608

Published: July 25, 2024

The combined inhibition of endoplasmic reticulum (ER) α-glucosidases I and II has been shown to inhibit replication a broad range viruses that rely on ER protein quality control. We found, by screening panel deoxynojirimycin cyclitol glycomimetics, the mechanism-based α-glucosidase inhibitor, 1,6-epi-cyclophellitol cyclosulfate, potently blocks SARS-CoV-2 in lung epithelial cells, halting intracellular generation mature spike protein, reducing production infectious progeny, leading reduced syncytium formation. Through activity-based profiling, we confirmed primary airway grown at air–liquid interface. 1,6-epi-Cyclophellitol cyclosulfate inhibits early pandemic more recent variants, as well SARS-CoV MERS-CoV. reported antiviral activity is comparable best-in-class described glucosidase inhibitors, all competitive inhibitors also targeting other glycoprocessing enzymes not involved propose selective blocking ER-resident covalent irreversible manner new strategy search for effective agents

Language: Английский

Citations

1
Conformational and Electronic Variations in 1,2‐ and 1,5a‐Cyclophellitols and their Impact on Retaining α‐Glucosidase Inhibition DOI Creative Commons
Tim P. Ofman,

Jurriaan J. A. Heming,

Alba Nin‐Hill

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(31)

Published: April 16, 2024

Glycoside hydrolases (glycosidases) take part in myriad biological processes and are important therapeutic targets. Competitive mechanism-based inhibitors useful tools to dissect their role comprise a good starting point for drug discovery. The natural product, cyclophellitol, mechanism-based, covalent irreversible retaining β-glucosidase inhibitor has inspired the design of diverse α- β-glycosidase activity-based probe scaffolds. Here, we sought deepen our understanding structural functional requirements cyclophellitol-type compounds effective human α-glucosidase inhibition. We synthesized comprehensive set α-configured 1,2- 1,5a-cyclophellitol analogues bearing variety electrophilic traps. inhibitory potency these was assessed towards both lysosomal ER α-glucosidases. These studies revealed 1,5a-cyclophellitols be most potent inhibitors, with nature electrophile determining mode action (covalent or non-covalent). DFT calculations support ability 1,5a-cyclophellitols, but not 1,2-congeners, adopt conformations that mimic either Michaelis complex transition state

Language: Английский

Citations

1
Trans-cyclosulfamidate mannose-configured cyclitol allows isoform-dependent inhibition of GH47 α-d-mannosidases through a bump–hole strategy DOI Creative Commons
Alexandra Males, Ken Kok, Alba Nin‐Hill

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(46), P. 13581 - 13586

Published: Jan. 1, 2023

1,6- Trans -manno-cyclosulfamidate 6 inhibits selectively an L310S mutant of Caulobacter GH47 α- d -mannosidase by virtue its 1 C 4 conformation and bump-and-hole strategy, enabling allele-specific inhibition within the α-mannosidase family.

Language: Английский

Citations

3