Dataset Information

Efficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac₅GalNTGc.

ABSTRACT: There is a critical need to develop small-molecule inhibitors of mucin-type O-linked glycosylation. The best-known reagent currently is benzyl-GalNAc, but it is effective only at millimolar concentrations. This article demonstrates that Ac₅GalNTGc, a peracetylated C-2 sulfhydryl-substituted GalNAc, fulfills this unmet need. When added to cultured leukocytes, breast cells, and prostate cells, Ac₅GalNTGc increased cell-surface VVA binding by ∼10-fold, indicating truncation of O-glycan biosynthesis. Cytometry, mass spectrometry, and western blot analysis of HL-60 promyelocytes demonstrated that 50-80 μM Ac₅GalNTGc prevented elaboration of 30%-60% of the O-glycans beyond the Tn-antigen (GalNAcα1-Ser/Thr) stage. The effect of the compound on N-glycans and glycosphingolipids was small. Glycan inhibition induced by Ac₅GalNTGc resulted in 50%-80% reduction in leukocyte sialyl-Lewis X expression and L-/P-selectin-mediated rolling under flow conditions. Ac₅GalNTGc was pharmacologically active in mouse. It reduced neutrophil infiltration to sites of inflammation by ∼60%. Overall, Ac₅GalNTGc may find diverse applications as a potent inhibitor of O-glycosylation.

SUBMITTER: Wang SS

PROVIDER: S-EPMC8140985 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac5GalNTGc.

Wang Shuen-Shiuan SS Solar Virginia Del VD Yu Xinheng X Antonopoulos Aristotelis A Friedman Alan E AE Agarwal Kavita K Garg Monika M Ahmed Syed Meheboob SM Addhya Ahana A Nasirikenari Mehrab M Lau Joseph T JT Dell Anne A Haslam Stuart M SM Sampathkumar Srinivasa-Gopalan SG Neelamegham Sriram S

Cell chemical biology 20210219 5

There is a critical need to develop small-molecule inhibitors of mucin-type O-linked glycosylation. The best-known reagent currently is benzyl-GalNAc, but it is effective only at millimolar concentrations. This article demonstrates that Ac5GalNTGc, a peracetylated C-2 sulfhydryl-substituted GalNAc, fulfills this unmet need. When added to cultured leukocytes, breast cells, and prostate cells, Ac5GalNTGc increased cell-surface VVA binding by ∼10-fold, indicating truncation of ...[more]

PMID: 33609441

Similar Datasets

Project description:Deep eutectic solvents (DESs) act as both an organic solvent and a useful catalyst for organic synthesis reactions, especially the synthesis of heterocyclic compounds containing the element nitrogen. DESs exhibit many important properties namely large liquid fields, biodegradability, outstanding thermal stability, and moderate vapor pressure. Amorphous carbon-bearing sulfonic acid groups (AC-SO3H) are one of the new-generation solid acids showing strong acid activity. Based on the simultaneous presence of acidic functional groups such as carboxylic acid, phenolic, and sulfonic acid groups, they exhibit many important activities namely strong Brønsted acid, high surface area, high stability, reusability, and recyclability. In this study, AC-SO3H was made from rice husk via the carbonization and sulfonation processes, and the surface properties and structure were examined using contemporary methods such as FT-IR, P-XRD, TGA, SEM, and EDS. And, [Urea]7[ZnCl2]2 was synthesized from urea and ZnCl2 with a mole ratio of 7 : 2; the structure is defined using FT-IR and TGA. By combining AC-SO3H and [Urea]7[ZnCl2]2 we aim to form an effective catalyst/solvent system for the preparation of polysubstituted imidazole derivatives through the multi-component cyclization reaction from nitrobenzenes, benzil, aldehydes, and ammonium acetate. The major products are obtained with high isolation yields above 60%. To assess the catalyst system's activity, the recovery and reusability of the AC-SO3H/[Urea]7[ZnCl2]2 system were examined with hardly any performance modification. In an effort to create potential enzyme α-glucosidase inhibitors, several novel polysubstituted imidazoles were created. Five of these compounds showed good enzyme α-glucosidase inhibitor activity. The most effective substances were IMI-13, IMI-15, and IMI-20, with IC50 values that were greater than the acarbose at 16.5, 15.8, and 11.6 μM, respectively - the acarbose (IC50, 214.5 μM) as the positive control.

Dataset Information

Efficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac₅GalNTGc.

Publications

Efficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac<sub>5</sub>GalNTGc.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets