Glycopolymer Inhibitors of Galectin-3 Suppress the Markers of Tissue Remodeling in Pulmonary Hypertension

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00586953" target="_blank" >RIV/61388971:_____/24:00586953 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/24:00586953 RIV/61389013:_____/24:00586953 RIV/68407700:21460/24:00382232 RIV/00216208:11310/24:10487995

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jmedchem.4c00341" target="_blank" >https://doi.org/10.1021/acs.jmedchem.4c00341</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.4c00341" target="_blank" >10.1021/acs.jmedchem.4c00341</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Glycopolymer Inhibitors of Galectin-3 Suppress the Markers of Tissue Remodeling in Pulmonary Hypertension

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Glycopolymer Inhibitors of Galectin-3 Suppress the Markers of Tissue Remodeling in Pulmonary Hypertension

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

1520-4804

Svazek periodika

67

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

9214-9226

Kód UT WoS článku

001238274000001

EID výsledku v databázi Scopus

2-s2.0-85195304229