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The Development of a High-Affinity Conformation-Sensitive Antibody Mimetic Using a Biocompatible Copolymer Carrier (iBody)
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SYSNO ASEP 0547609 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The Development of a High-Affinity Conformation-Sensitive Antibody Mimetic Using a Biocompatible Copolymer Carrier (iBody) Author(s) Blažková, Kristýna (UOCHB-X) ORCID, RID
Beranová, Jana (UOCHB-X) ORCID
Hradilek, Martin (UOCHB-X) ORCID
Kostka, Libor (UMCH-V) RID, ORCID
Šubr, Vladimír (UMCH-V) RID, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCID
Šácha, Pavel (UOCHB-X) RID, ORCID
Konvalinka, Jan (UOCHB-X) RID, ORCIDArticle number 101342 Source Title Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 297, č. 5 (2021)Number of pages 11 s. Language eng - English Country US - United States Keywords antibody mimetics ; bicyclic phage display ; molecular recognition ; HPMA copolymer ; PSMA ; phage display ; cyclic peptide ; protein targeting ; nanotechnology ; chemical biology OECD category Biochemistry and molecular biology R&D Projects GA21-04166S GA ČR - Czech Science Foundation (CSF) GA19-05649S GA ČR - Czech Science Foundation (CSF) EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 ; UMCH-V - RVO:61389013 UT WOS 000723119000013 EID SCOPUS 85120041008 DOI 10.1016/j.jbc.2021.101342 Annotation Peptide display methods are a powerful tool for discovering new ligands of pharmacologically relevant targets. However, the selected ligands often suffer from low affinity. Using phage display, we identified a new bicyclic peptide binder of prostate specific membrane antigen (PSMA), a metalloprotease frequently overexpressed in prostate cancer. We show that linking multiple copies of a selected low affinity peptide to a biocompatible water-soluble N-(2-hydroxypropyl)methacrylamide copolymer carrier (iBody) improved binding of the conjugate by several orders of magnitude. Furthermore, using ELISA, enzyme kinetics, confocal microscopy and other approaches we demonstrate that the resulting iBody can distinguish between different conformations of the target protein. The possibility to develop stable, fully synthetic, conformation-selective antibody mimetics has potential applications for molecular recognition, diagnosis and treatment of many pathologies. This strategy could significantly contribute to more effective drug discovery and design. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2022 Electronic address https://doi.org/10.1016/j.jbc.2021.101342
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