Advanced high-affinity glycoconjugate ligands of galectins

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00567424" target="_blank" >RIV/61388963:_____/23:00567424 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/23:00567424 RIV/68407700:21460/23:00365026 RIV/00216208:11310/23:10454003

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S004520682200685X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S004520682200685X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2022.106279" target="_blank" >10.1016/j.bioorg.2022.106279</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Advanced high-affinity glycoconjugate ligands of galectins

Popis výsledku v původním jazyce

Galectins are proteins of the family of human lectins. By binding terminal galactose units of cell surface glycans, they moderate biological and pathological processes such as cell signaling, cell adhesion, apoptosis, fibrosis, carcinogenesis, and metabolic disorders. The binding of monovalent glycans to galectins is usually relatively weak. Therefore, the presentation of carbohydrate ligands on multivalent scaffolds can efficiently increase and/ or discriminate the affinity of the glycoconjugate to different galectins. A library of glycoclusters and glyco-dendrimers with various structural presentations of the common functionalized N-acetyllactosamine ligand was prepared to evaluate how the mode of presentation affects the affinity and selectivity to the two most abundant galectins, galectin-1 (Gal-1) and galectin-3 (Gal-3). In addition, the effect of a one-to two-unit carbohydrate spacer on the affinity of the glycoconjugates was determined. A new design of the biolayer interferometry (BLI) method with specific AVI-tagged constructs was used to determine the affinity to galectins, and compared with the gold-standard method of isothermal titration calorimetry (ITC). This study reveals new routes to low nanomolar glycoconjugate inhibitors of galectins of interest for biomedical research.

Název v anglickém jazyce

Advanced high-affinity glycoconjugate ligands of galectins

Popis výsledku anglicky

Galectins are proteins of the family of human lectins. By binding terminal galactose units of cell surface glycans, they moderate biological and pathological processes such as cell signaling, cell adhesion, apoptosis, fibrosis, carcinogenesis, and metabolic disorders. The binding of monovalent glycans to galectins is usually relatively weak. Therefore, the presentation of carbohydrate ligands on multivalent scaffolds can efficiently increase and/ or discriminate the affinity of the glycoconjugate to different galectins. A library of glycoclusters and glyco-dendrimers with various structural presentations of the common functionalized N-acetyllactosamine ligand was prepared to evaluate how the mode of presentation affects the affinity and selectivity to the two most abundant galectins, galectin-1 (Gal-1) and galectin-3 (Gal-3). In addition, the effect of a one-to two-unit carbohydrate spacer on the affinity of the glycoconjugates was determined. A new design of the biolayer interferometry (BLI) method with specific AVI-tagged constructs was used to determine the affinity to galectins, and compared with the gold-standard method of isothermal titration calorimetry (ITC). This study reveals new routes to low nanomolar glycoconjugate inhibitors of galectins of interest for biomedical research.

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

2023

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

1090-2120

Svazek periodika

131

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

106279

Kód UT WoS článku

000907594900004

EID výsledku v databázi Scopus

2-s2.0-85142708682