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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00547609" target="_blank" >RIV/61388963:_____/21:00547609 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389013:_____/21:00547609 RIV/00216208:11110/21:10436496 RIV/00216208:11310/21:10436496

Výsledek na webu

<a href="https://doi.org/10.1016/j.jbc.2021.101342" target="_blank" >https://doi.org/10.1016/j.jbc.2021.101342</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2021.101342" target="_blank" >10.1016/j.jbc.2021.101342</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

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

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Svazek periodika

297

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

101342

Kód UT WoS článku

000723119000013

EID výsledku v databázi Scopus

2-s2.0-85120041008