Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F11%3A10107632" target="_blank" >RIV/00216208:11310/11:10107632 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/11:00369329 RIV/61388963:_____/11:00369329
Result on the web
<a href="http://dx.doi.org/10.1021/jm200807m" target="_blank" >http://dx.doi.org/10.1021/jm200807m</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/jm200807m" target="_blank" >10.1021/jm200807m</a>

Result language
angličtina
Original language name
Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity
Original language description
We report the identification and characterization of GCPII inhibitors with enhanced liphophilicity that are derived from a series of newly identified dipeptidic GCPII substrates featuring nonpolar aliphatic side chains at the C-terminus. To analyze the interactions governing the substrate recognition by GCPII, we determined crystal structures of the inactive GCPII(E424A) mutant in complex with selected dipeptides and complemented the structural data with quantum mechanics/molecular mechanics calculations. On the basis of those data, we designed, synthesized, and evaluated a series of novel GCPII inhibitors with enhanced lipophilicity, with the best candidates having low nanomolar inhibition constants and clogD } -0.3. Our findings offer new insights into the design of more lipophilic inhibitors targeting GCPII
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
S - Specificky vyzkum na vysokych skolach

Publication year
2011
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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