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

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
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 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 (en)
Title	Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity (en)
skos:prefLabel	Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity (en)
skos:notation	RIV/86652036:_____/11:00369329!RIV12-AV0-86652036
http://linked.open...avai/predkladatel	Biotechnologický ústav AV ČR, v. v. i.
http://linked.open...avai/riv/aktivita	P S Z
http://linked.open...avai/riv/aktivity	P(LC512), P(ME10031), S, Z(AV0Z40550506), Z(AV0Z50520701)
http://linked.open...iv/cisloPeriodika	21
http://linked.open...vai/riv/dodaniDat	2012
http://linked.open...aciTvurceVysledku	Bařinka, Cyril Alquicer, Glenda Škultétyová, Ľubica
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Biotechnologický ústav AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	216616
http://linked.open...ai/riv/idVysledku	RIV/86652036:_____/11:00369329
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Glutamate carboxypeptidase II.; QM/MM calculations; X-ray crystallography; lipophilicity; inhibitors (en)
http://linked.open.../riv/klicoveSlovo	X-ray crystallography inhibitors lipophilicity Glutamate carboxypeptidase II. QM/MM calculations
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[158CD8642DFA]
http://linked.open...i/riv/nazevZdroje	Journal of Medicinal Chemistry
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	3 (xsd:int)
http://linked.open...cetTvurcuVysledku	14 (xsd:int)
http://linked.open...vavai/riv/projekt	Center for biomolecules and complex molecular systems Structure-based design of ligands and inhibitors targeting glutamate carboxypeptidase II and its homologs
http://linked.open...UplatneniVysledku	2011
http://linked.open...v/svazekPeriodika	54
http://linked.open...iv/tvurceVysledku	Konvalinka, Jan Rulíšek, Lubomír Alquicer, Glenda Bařinka, Cyril Byun, Y. Kim, H.-J. Lubkowski, J. Mease, R. Mlčochová, Petra Navrátil, Michal Němcová, Adriana Plechanovová, Anna Pomper, M. Škultétyová, Ľubica
http://linked.open...ain/vavai/riv/wos	000296408100010
http://linked.open...n/vavai/riv/zamer	Regulace biologických procesů: Chemické modulátory vybraných systémů významných pro medicínu a zemědělství Establishing of the Biotechnology Institute ASCR
issn	0022-2623
number of pages	12 (xsd:int)
http://bibframe.org/vocab/doi	10.1021/jm200807m
is http://linked.open...avai/riv/vysledek of	Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity Novel Substrate-Based Inhibitors of Human Glutamate Carboxypeptidase II with Enhanced Lipophilicity

Faceted Search & Find service v1.16.118 as of Jun 21 2024

Alternative Linked Data Documents: ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3240 as of Jun 21 2024, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (126 GB total memory, 48 GB memory in use)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software