Počet záznamů: 1
Human interleukin-23 receptor antagonists derived from an albumin-binding domain scaffold inhibit IL-23-dependent ex vivo expansion of IL-17-producing T-cells
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SYSNO ASEP 0431238 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Human interleukin-23 receptor antagonists derived from an albumin-binding domain scaffold inhibit IL-23-dependent ex vivo expansion of IL-17-producing T-cells Tvůrce(i) Kuchař, Milan (BTO-N) RID
Vaňková, Lucie (BTO-N)
Petroková, Hana (BTO-N) RID
Černý, Jiří (BTO-N) RID, ORCID
Osička, Radim (MBU-M) RID, ORCID
Pelák, O. (CZ)
Šípová, Hana (URE-Y)
Schneider, Bohdan (BTO-N) RID, ORCID
Homola, Jiří (URE-Y) RID
Šebo, Peter (BTO-N)
Kalina, T. (CZ)
Malý, Petr (BTO-N) RID, ORCIDZdroj.dok. Proteins-Structure, Function and Bioinformatics. - : Wiley - ISSN 0887-3585
Roč. 82, č. 6 (2014), s. 975-989Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova ribosome display ; combinatorial library ; psoriasis Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP303/10/1849 GA ČR - Grantová agentura ČR GAP302/11/0580 GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora BTO-N - RVO:86652036 ; MBU-M - RVO:61388971 ; URE-Y - RVO:67985882 CEZ AV0Z50520701 - BTO-N (2007-2013) UT WOS 000335955300009 DOI 10.1002/prot.24472 Anotace Engineered combinatorial libraries derived from small protein scaffolds represent a powerful tool for generating novel binders with high affinity, required specificity and designed inhibitory function. This work was aimed to generate a collection of recombinant binders of human interleukin-23 receptor (IL-23R), which is a key element of proinflammatory IL-23-mediated signaling. A library of variants derived from the three-helix bundle scaffold of the albumin-binding domain (ABD) of streptococcal protein G and ribosome display were used to select for high-affinity binders of recombinant extracellular IL-23R. A collection of 34 IL-23R-binding proteins (called REX binders), corresponding to 18 different sequence variants, was used to identify a group of ligands that inhibited binding of the recombinant p19 subunit of IL-23, or the biologically active human IL-23 cytokine, to the recombinant IL-23R or soluble IL-23R-IgG chimera. The strongest competitors for IL-23R binding in ELISA were confirmed to recognize human IL-23R-IgG in surface plasmon resonance experiments, estimating the binding affinity in the sub- to nanomolar range. We further demonstrated that several REX variants bind to human leukemic cell lines K-562, THP-1 and Jurkat, and this binding correlated with IL-23R cell-surface expression. The REX125, REX009 and REX128 variants competed with the p19 protein for binding to THP-1 cells. Moreover, the presence of REX125, REX009 and REX115 variants significantly inhibited the IL-23-driven expansion of IL-17-producing primary human CD4(+) T-cells. Thus, we conclude that unique IL-23R antagonists derived from the ABD scaffold were generated that might be useful in designing novel anti-inflammatory biologicals. Proteins 2014; 82:975-989. (c) 2013 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2015
Počet záznamů: 1