• Je něco špatně v tomto záznamu ?

Molecular recognition of fibroblast activation protein for diagnostic and therapeutic applications

A. Šimková, P. Bušek, A. Šedo, J. Konvalinka,

. 2020 ; 1868 (7) : 140409. [pub] 20200406

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články, práce podpořená grantem, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/bmc20024915

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

000      
00000naa a2200000 a 4500
001      
bmc20024915
003      
CZ-PrNML
005      
20201222160031.0
007      
ta
008      
201125s2020 ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.bbapap.2020.140409 $2 doi
035    __
$a (PubMed)32171757
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Šimková, Adéla $u Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, 166 10 Praha 6, Czech Republic; Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 12843 Praha 2, Czech Republic. Electronic address: adela.simkova@uochb.cas.cz.
245    10
$a Molecular recognition of fibroblast activation protein for diagnostic and therapeutic applications / $c A. Šimková, P. Bušek, A. Šedo, J. Konvalinka,
520    9_
$a 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.
650    _2
$a katalytická doména $7 D020134
650    _2
$a dipeptidylpeptidasa 4 $x metabolismus $7 D018819
650    _2
$a fibroblasty $x metabolismus $7 D005347
650    _2
$a želatinasy $x chemie $x účinky léků $x metabolismus $7 D018093
650    _2
$a lidé $7 D006801
650    _2
$a membránové proteiny $x chemie $x účinky léků $x metabolismus $7 D008565
650    _2
$a molekulární struktura $7 D015394
650    _2
$a nádory $x diagnóza $x metabolismus $x terapie $7 D009369
650    _2
$a prekurzory léčiv $7 D011355
650    _2
$a serinové endopeptidasy $x chemie $x účinky léků $x metabolismus $7 D012697
650    _2
$a substrátová specifita $7 D013379
650    _2
$a nádorové mikroprostředí $7 D059016
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
655    _2
$a přehledy $7 D016454
700    1_
$a Bušek, Petr $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Praha 2, Czech Republic. Electronic address: petr.busek2@lf1.cuni.cz.
700    1_
$a Šedo, Aleksi $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Praha 2, Czech Republic. Electronic address: aleksi@cesnet.cz.
700    1_
$a Konvalinka, Jan $u Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, 166 10 Praha 6, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8, 12843 Praha 2, Czech Republic. Electronic address: jan.konvalinka@uochb.cas.cz.
773    0_
$w MED00007006 $t Biochimica et biophysica acta. Proteins and proteomics $x 1878-1454 $g Roč. 1868, č. 7 (2020), s. 140409
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32171757 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20201125 $b ABA008
991    __
$a 20201222160027 $b ABA008
999    __
$a ok $b bmc $g 1599060 $s 1115601
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 1868 $c 7 $d 140409 $e 20200406 $i 1878-1454 $m Biochimica et biophysica acta. Proteins and proteomics $n Biochem Biophys Acta $x MED00007006
LZP    __
$a Pubmed-20201125

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace