Targeting galectin-4 with glycoconjugates of varying architectures: a multivalency étude with accent on anti-tumor effect and protection against apoptosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00639544" target="_blank" >RIV/61388963:_____/25:00639544 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/25:00639544 RIV/68407700:21460/25:00389989 RIV/00216208:11310/25:10503720

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0223523425009146?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523425009146?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2025.118149" target="_blank" >10.1016/j.ejmech.2025.118149</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Targeting galectin-4 with glycoconjugates of varying architectures: a multivalency étude with accent on anti-tumor effect and protection against apoptosis

Popis výsledku v původním jazyce

Galectin-4 (Gal-4) is a protumorigenic protein that strongly participates especially in gastrointestinal cancer and is increasingly recognized as a therapeutic target in gastrointestinal malignancies, where its dysregulated expression contributes to tumor progression and immune modulation. Its abundance and the extent of its involvement in these pathologies are comparable with its much better-studied counterparts, galectin-1 and3. However, to date, no systematic effort has been made to design efficient defined Gal-4 inhibitors with a potential therapeutic effect. In this work, we present a library of biocompatible multivalent Gal-4 inhibitors with diverse architectures to investigate how different modes of multivalent presentation of a common ligand, lactose, influence the binding affinity to Gal-4. The most efficient scaffold was then loaded with a high-affinity tetrasaccharide ligand of Gal-4, derived from lacto-N-tetraose, to further enhance Gal-4 binding. The resulting glycopolymer exhibited outstanding performance in inhibiting Gal-4-induced apoptosis of T lymphocytes, and, in addition, it efficiently scavenged Gal-4 from the surface of cancer cells. Both of these processes are relevant for tumor immune evasion. Given the high biocompatibility, and low toxicity of the POx carrier, this glycopolymer has a strong potential as a candidate for further development of glycotherapeutics against Gal-4-associated diseases such as gastrointestinal cancer.

Název v anglickém jazyce

Targeting galectin-4 with glycoconjugates of varying architectures: a multivalency étude with accent on anti-tumor effect and protection against apoptosis

Popis výsledku anglicky

Galectin-4 (Gal-4) is a protumorigenic protein that strongly participates especially in gastrointestinal cancer and is increasingly recognized as a therapeutic target in gastrointestinal malignancies, where its dysregulated expression contributes to tumor progression and immune modulation. Its abundance and the extent of its involvement in these pathologies are comparable with its much better-studied counterparts, galectin-1 and3. However, to date, no systematic effort has been made to design efficient defined Gal-4 inhibitors with a potential therapeutic effect. In this work, we present a library of biocompatible multivalent Gal-4 inhibitors with diverse architectures to investigate how different modes of multivalent presentation of a common ligand, lactose, influence the binding affinity to Gal-4. The most efficient scaffold was then loaded with a high-affinity tetrasaccharide ligand of Gal-4, derived from lacto-N-tetraose, to further enhance Gal-4 binding. The resulting glycopolymer exhibited outstanding performance in inhibiting Gal-4-induced apoptosis of T lymphocytes, and, in addition, it efficiently scavenged Gal-4 from the surface of cancer cells. Both of these processes are relevant for tumor immune evasion. Given the high biocompatibility, and low toxicity of the POx carrier, this glycopolymer has a strong potential as a candidate for further development of glycotherapeutics against Gal-4-associated diseases such as gastrointestinal cancer.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical 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

2025

Kód důvěrnosti údajů

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

Název periodika

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

1768-3254

Svazek periodika

300

Číslo periodika v rámci svazku

15 Dec

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

12

Strana od-do

118149

Kód UT WoS článku

001583014200001

EID výsledku v databázi Scopus

2-s2.0-105015645847