Molecular recognition of fibroblast activation protein for diagnostic and therapeutic applications
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
32171757
DOI
10.1016/j.bbapap.2020.140409
PII: S1570-9639(20)30054-6
Knihovny.cz E-zdroje
- Klíčová slova
- Activity-based probes, Cancer tissue targeting, FAP inhibitors, FAP substrates, Fibroblast activation protein,
- MeSH
- dipeptidylpeptidasa 4 metabolismus MeSH
- endopeptidasy MeSH
- fibroblasty metabolismus MeSH
- katalytická doména MeSH
- lidé MeSH
- membránové proteiny chemie účinky léků metabolismus MeSH
- molekulární struktura MeSH
- nádorové mikroprostředí MeSH
- nádory diagnóza metabolismus terapie MeSH
- prekurzory léčiv MeSH
- prolyloligopeptidasy MeSH
- serinové endopeptidasy chemie účinky léků metabolismus MeSH
- substrátová specifita MeSH
- želatinasy chemie účinky léků metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- dipeptidylpeptidasa 4 MeSH
- DPP4 protein, human MeSH Prohlížeč
- endopeptidasy MeSH
- fibroblast activation protein alpha MeSH Prohlížeč
- membránové proteiny MeSH
- prekurzory léčiv MeSH
- PREPL protein, human MeSH Prohlížeč
- prolyloligopeptidasy MeSH
- serinové endopeptidasy MeSH
- želatinasy MeSH
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.
Citace poskytuje Crossref.org
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