High-affinity N-(2-hydroxypropyl)methacrylamide copolymers with tailored N-acetyllactosamine presentation discriminate between galectins

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00521956" target="_blank" >RIV/61388971:_____/20:00521956 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389013:_____/20:00521956 RIV/68407700:21460/20:00339098

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.biomac.9b01370" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.biomac.9b01370</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.biomac.9b01370" target="_blank" >10.1021/acs.biomac.9b01370</a>

Jazyk výsledku

angličtina

Název v původním jazyce

High-affinity N-(2-hydroxypropyl)methacrylamide copolymers with tailored N-acetyllactosamine presentation discriminate between galectins

Popis výsledku v původním jazyce

N-Acetyllactosamine (LacNAc, Galβ4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen N-(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3. The controlled radical reversible addition–fragmentation chain transfer copolymerization technique afforded linear polymer precursors with comparable molecular weight (Mn ≈ 22,000 g mol–1) and narrow dispersity (D̵ ≈ 1.1). The precursors were conjugated with the functionalized LacNAc disaccharide (4–22 mol % content in glycopolymer) prepared by enzymatic synthesis under catalysis by β-galactosidase from Bacillus circulans. The structure–affinity relationship study based on the enzyme-linked immunosorbent assay revealed that the type of LacNAc presentation, individual or clustered on bi- or trivalent linkers, brings a clear discrimination (almost 300-fold) between Gal-1 and Gal-3, reaching avidity to Gal-1 in the nanomolar range. Whereas Gal-1 strongly preferred a dense presentation of individually distributed LacNAc epitopes, Gal-3 preferred a clustered LacNAc presentation. Such a strong galectin preference based just on the structure of a multivalent glycopolymer type is exceptional. The prepared nontoxic, nonimmunogenic, and biocompatible glycopolymers are prospective for therapeutic applications requiring selectivity for one particular galectin.

Název v anglickém jazyce

High-affinity N-(2-hydroxypropyl)methacrylamide copolymers with tailored N-acetyllactosamine presentation discriminate between galectins

Popis výsledku anglicky

N-Acetyllactosamine (LacNAc, Galβ4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen N-(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3. The controlled radical reversible addition–fragmentation chain transfer copolymerization technique afforded linear polymer precursors with comparable molecular weight (Mn ≈ 22,000 g mol–1) and narrow dispersity (D̵ ≈ 1.1). The precursors were conjugated with the functionalized LacNAc disaccharide (4–22 mol % content in glycopolymer) prepared by enzymatic synthesis under catalysis by β-galactosidase from Bacillus circulans. The structure–affinity relationship study based on the enzyme-linked immunosorbent assay revealed that the type of LacNAc presentation, individual or clustered on bi- or trivalent linkers, brings a clear discrimination (almost 300-fold) between Gal-1 and Gal-3, reaching avidity to Gal-1 in the nanomolar range. Whereas Gal-1 strongly preferred a dense presentation of individually distributed LacNAc epitopes, Gal-3 preferred a clustered LacNAc presentation. Such a strong galectin preference based just on the structure of a multivalent glycopolymer type is exceptional. The prepared nontoxic, nonimmunogenic, and biocompatible glycopolymers are prospective for therapeutic applications requiring selectivity for one particular galectin.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Biomacromolecules

ISSN

1525-7797

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

641-652

Kód UT WoS článku

000513091100036

EID výsledku v databázi Scopus

2-s2.0-85079203166