The Development of a High-Affinity Conformation-Sensitive Antibody Mimetic Using a Biocompatible Copolymer Carrier (iBody)

0547609 - ÚOCHB 2022 RIV US eng J - Journal Article
Blažková, Kristýna - Beranová, Jana - Hradilek, Martin - Kostka, Libor - Šubr, Vladimír - Etrych, Tomáš - Šácha, Pavel - Konvalinka, Jan
The Development of a High-Affinity Conformation-Sensitive Antibody Mimetic Using a Biocompatible Copolymer Carrier (iBody).
Journal of Biological Chemistry. Roč. 297, č. 5 (2021), č. článku 101342. ISSN 0021-9258. E-ISSN 1083-351X
R&D Projects: GA ČR(CZ) GA21-04166S; GA ČR(CZ) GA19-05649S; GA MŠMT(CZ) EF16_019/0000729
Institutional support: RVO:61388963 ; RVO:61389013
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; Polymer science (UMCH-V)
Impact factor: 5.485, year: 2021
Method of publishing: Open access
https://doi.org/10.1016/j.jbc.2021.101342

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.
Permanent Link: http://hdl.handle.net/11104/0323818