Molecular recognition of fibroblast activation protein for diagnostic and therapeutic applications

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00523934" target="_blank" >RIV/61388963:_____/20:00523934 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/20:10411646 RIV/00216208:11310/20:10411646

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S1570963920300546" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S1570963920300546</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbapap.2020.140409" target="_blank" >10.1016/j.bbapap.2020.140409</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular recognition of fibroblast activation protein for diagnostic and therapeutic applications

Popis výsledku v původním jazyce

Fibroblast activation protein (FAP) is a non-classical serine protease expressed predominantly in conditions accompanied by tissue remodeling, particularly cancer. Due to its plasma membrane localization, FAP represents a promising molecular target for tumor imaging and treatment. The unique enzymatic activity of FAP facilitates development of diagnostic and therapeutic tools based on molecular recognition of FAP by substrates and small-molecule inhibitors, in addition to conventional antibody-based strategies. In this review, we provide background on the pathophysiological role of FAP and discuss its potential for diagnostic and therapeutic applications. Furthermore, we present a detailed analysis of the structural patterns crucial for substrate and inhibitor recognition by the FAP active site and determinants of selectivity over the related proteases dipeptidyl peptidase IV and prolyl endopeptidase. We also review published data on targeting of the tumor microenvironment with FAP antibodies, FAP-targeted prodrugs, activity-based probes and small-molecule inhibitors. We describe use of a recently developed, selective FAP inhibitor with low-nanomolar potency in inhibitor-based targeting strategies including synthetic antibody mimetics based on hydrophilic polymers and inhibitor conjugates for PET imaging. In conclusion, recent advances in understanding of the molecular structure and function of FAP have significantly contributed to the development of several tools with potential for translation into clinical practice.

Název v anglickém jazyce

Molecular recognition of fibroblast activation protein for diagnostic and therapeutic applications

Popis výsledku anglicky

Fibroblast activation protein (FAP) is a non-classical serine protease expressed predominantly in conditions accompanied by tissue remodeling, particularly cancer. Due to its plasma membrane localization, FAP represents a promising molecular target for tumor imaging and treatment. The unique enzymatic activity of FAP facilitates development of diagnostic and therapeutic tools based on molecular recognition of FAP by substrates and small-molecule inhibitors, in addition to conventional antibody-based strategies. In this review, we provide background on the pathophysiological role of FAP and discuss its potential for diagnostic and therapeutic applications. Furthermore, we present a detailed analysis of the structural patterns crucial for substrate and inhibitor recognition by the FAP active site and determinants of selectivity over the related proteases dipeptidyl peptidase IV and prolyl endopeptidase. We also review published data on targeting of the tumor microenvironment with FAP antibodies, FAP-targeted prodrugs, activity-based probes and small-molecule inhibitors. We describe use of a recently developed, selective FAP inhibitor with low-nanomolar potency in inhibitor-based targeting strategies including synthetic antibody mimetics based on hydrophilic polymers and inhibitor conjugates for PET imaging. In conclusion, recent advances in understanding of the molecular structure and function of FAP have significantly contributed to the development of several tools with potential for translation into clinical practice.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Biochimica Et Biophysica Acta-Proteins and Proteomics

ISSN

1570-9639

e-ISSN

—

Svazek periodika

1868

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

17

Strana od-do

140409

Kód UT WoS článku

000528200000003

EID výsledku v databázi Scopus

2-s2.0-85082828207