High-affinity N-(2-hydroxypropyl)methacrylamide copolymers with tailored N-acetyllactosamine presentation discriminate between galectins
The result's identifiers
Result code in 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>
Alternative codes found
RIV/61389013:_____/20:00521956 RIV/68407700:21460/20:00339098
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
High-affinity N-(2-hydroxypropyl)methacrylamide copolymers with tailored N-acetyllactosamine presentation discriminate between galectins
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10404 - Polymer science
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomacromolecules
ISSN
1525-7797
e-ISSN
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Volume of the periodical
21
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
641-652
UT code for WoS article
000513091100036
EID of the result in the Scopus database
2-s2.0-85079203166