0586953 - FGÚ 2025 RIV US eng J - Journal Article
Sedlář, Antonín - Vrbata, David - Pokorná, Kateřina - Holzerová, Kristýna - Červený, Jakub - Kočková, Olga - Hlaváčková, Markéta - Doubková, Martina - Musílková, Jana - Křen, Vladimír - Kolář, František - Bačáková, Lucie - Bojarová, Pavla
Glycopolymer Inhibitors of Galectin-3 Suppress the Markers of Tissue Remodeling in Pulmonary Hypertension.
Journal of Medicinal Chemistry. Roč. 67, č. 11 (2024), s. 9214-9226. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA ČR(CZ) GA22-00317S; GA MŠMT(CZ) EH22_008/0004597; GA MŠMT(CZ) LUC23148
Institutional support: RVO:67985823 ; RVO:61388971 ; RVO:61389013
Keywords : in-vitro * poly(ethylene glycol) * poly(2-ethyl-2-oxazoline) * glycoproteins * cytotoxicity * well
OECD category: Respiratory systems; Organic chemistry (MBU-M); Polymer science (UMCH-V)
Impact factor: 6.9, year: 2023 ; AIS: 1.652, rok: 2023
Method of publishing: Open access
Result website:
https://doi.org/10.1021/acs.jmedchem.4c00341DOI: https://doi.org/10.1021/acs.jmedchem.4c00341

Pulmonary hypertension is a cardiovascular disease with a low survival rate. The protein galectin-3 (Gal-3) binding beta-galactosides of cellular glycoproteins plays an important role in the onset and development of this disease. Carbohydrate-based drugs that target Gal-3 represent a new therapeutic strategy in the treatment of pulmonary hypertension. Here, we present the synthesis of novel hydrophilic glycopolymer inhibitors of Gal-3 based on a polyoxazoline chain decorated with carbohydrate ligands. Biolayer interferometry revealed a high binding affinity of these glycopolymers to Gal-3 in the subnanomolar range. In the cell cultures of cardiac fibroblasts and pulmonary artery smooth muscle cells, the most potent glycopolymer 18 (Lac-high) caused a decrease in the expression of markers of tissue remodeling in pulmonary hypertension. The glycopolymers were shown to penetrate into the cells. In a biodistribution and pharmacokinetics study in rats, the glycopolymers accumulated in heart and lung tissues, which are most affected by pulmonary hypertension.
Permanent Link: https://hdl.handle.net/11104/0354633