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National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Development of analytical tools for quantification and screening for inhibitors of glutamate carboxypeptidases II and III
 Navrátil, Václav ; Konvalinka, Jan (advisor) ; Obšil, Tomáš (referee) ; Šedo, Aleksi (referee)
Glutamate carboxypeptidase II (GCPII) usually called prostate specific membrane antigen (PSMA) is membrane bound metallopeptidase expressed mainly in prostate carcinoma (PCa). Agents targeting GCPII suitable for both imaging and treatment of PCa are in development and they show promising results in advanced clinical trials. Some studies showed that GCPII may serve also as PCa blood serum marker, but this has not been validated due to the lack of methods suitable for accurate detection of GCPII in human blood. Moreover, GCPII is also expressed in brain, where it cleaves inhibitory N-acetyl-α-L- aspartyl-L-glutamate (NAAG) to release excitatory L-glutamate and GCPII inhibition has been shown to be neuroprotective in animal models of several neuropathies. Tight binding inhibitors of GCPII have been identified by rational design, but all have poor bioavailability and thus cannot be used in clinics. Identifying new scaffolds by 'brute force' screening methods is thus essential; however, no such method for GCPII has been developed so far. Glutamate carboxypeptidase III (GCPIII) is also expressed in brain and cleaves NAAG. It is thus an important protein for understanding of GCPII function as well as GCPII targeting in medicine. Here, we focused on development of novel methods for quantification of both...
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Structural Studies of anti-CA IX Monoclonal Antibody M75 Fab Fragment in Complex with its Epitope Peptide
 Mader, Pavel ; Štouračová, Renata ; Brynda, Jiří ; Závada, Jan
CA IX is a cell surface protein that exerts capacity of binding cell surface receptors, and is associated with several types of human carcinomas. Monoclonal antibody M75 recognizes specifically an epitope identified as six repeats of amino acid sequence PGEEDLP, localized in the proteoglycan like domain of CA IX. Structural study of the M75 Fab fragment in complex with its epitope peptide PGEEDLPGEEDL is presented.
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