Design and development of novel reagents, tools, and techniques targeting human glutamate carboxypeptidases II and III

Project Information

GCPII_SYSTEM

Grant agreement ID: 249220

Project closed

Start date 1 November 2010

End date 31 October 2014

Funded under

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Total cost € 100 000,00

EU contribution € 100 000,00

Coordinated by

BIOTECHNOLOGICKY USTAV AV CR VVI
Czechia

Objective

Glutamate carboxypeptidase II (GCPII) is a membrane-bound metallopeptidase with a vast pharmacological potential. Given the intimate involvement of the enzyme in neurotransmission under normal physiological conditions, it is not surprising that GCPII-specific inhibitors are neuroprotective in multiple preclinical models of neurodegeneration. Additionally, the cancer-associated form of GCPII is exploited as a target for immunotherapy/imaging of prostate cancer as well as neovasculature of solid tumors. Despite of its utilization in (pre)clinical settings, the physiological function of GCPII in the latter tissues is unknown and the whole picture is further complicated by the existence of GCPIII, a close GCPII homolog. The main goals of this proposal focus on the identification and development of novel reagents, tools and techniques associated with the GCPII/GCPIII system that may help addressing questions pertaining to the fundamental (patho)physiological roles of GCPII/GCPIII. We will use information from X-ray structures of GCPII/GCPIII complexes to modify and improve characteristics of small-molecule ligands currently used in experimental models of prostate cancer. Secondly, will develop an activity assay based on fluorescence polarization that, in turn, will be exploited for the identification of novel inhibitor scaffolds targeting GCPII/GCPIII. The physicochemical properties of the lead-like compounds will be further optimized to develop isoform (GCPII vs. GCPIII) specific reagents. Such compounds are not available at present and their availability is crucial for dissecting potentially diverse physiological functions of GCPIII and GCPII with implications for GCPII/III associated pathologies. Lastly, we will try to gain insight into non-enzymatic (receptor-like) properties of GCPII by identifying physiological interaction partner(s) of the enzyme using a tandem affinity purification approach.

Fields of science

• natural sciences › biological sciences › neurobiology
• medical and health sciences › clinical medicine › oncology › prostate cancer
• medical and health sciences › basic medicine › pathology
• medical and health sciences › basic medicine › immunology › immunotherapy
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes

Programme(s)

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

• FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants"

Call for proposal

FP7-PEOPLE-2009-RG
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

BIOTECHNOLOGICKY USTAV AV CR VVI

Administrative Contact

Jan Skoda (Dr.)

• EU contribution: € 100 000,00
• Address: PRUMYSLOVA 595 ; 252 50 Vestec ; Czechia
• Region: Česko › Střední Čechy › Středočeský kraj
• Activity type: Other
• Total cost: No data