About: Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase

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About: Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase 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)

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://dx.doi.org/10.1016/j.bmc.2012.01.037
Description	Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic applications in the treatment of numerous neurodegenerative diseases. Here we report the synthesis and evaluation of a series of inhibitors designed to have increased cell membrane permeability via intramolecular hydrogen bonding. Their potencies were examined in both purified enzyme and cell-based assays; a comparison of these results demonstrates that two of the new inhibitors display significantly increased membrane permeability over previous analogs. NMR spectroscopy provides evidence of intramolecular hydrogen bonding under physiological conditions in two of the inhibitors. Crystal structures of the inhibitors in the nNOS active site confirm the predicted non-intramolecular hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective approach for increasing cell membrane permeability without affecting target protein binding. (C) 2012 Elsevier Ltd. All rights reserved. Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic applications in the treatment of numerous neurodegenerative diseases. Here we report the synthesis and evaluation of a series of inhibitors designed to have increased cell membrane permeability via intramolecular hydrogen bonding. Their potencies were examined in both purified enzyme and cell-based assays; a comparison of these results demonstrates that two of the new inhibitors display significantly increased membrane permeability over previous analogs. NMR spectroscopy provides evidence of intramolecular hydrogen bonding under physiological conditions in two of the inhibitors. Crystal structures of the inhibitors in the nNOS active site confirm the predicted non-intramolecular hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective approach for increasing cell membrane permeability without affecting target protein binding. (C) 2012 Elsevier Ltd. All rights reserved. (en)
Title	Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase (en)
skos:prefLabel	Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase (en)
skos:notation	RIV/00064165:_____/12:11398!RIV13-MZ0-00064165
http://linked.open...avai/predkladatel	Všeobecná fakultní nemocnice v Praze
http://linked.open...avai/riv/aktivita	I Z
http://linked.open...avai/riv/aktivity	I, Z(MSM0021620849)
http://linked.open...iv/cisloPeriodika	7
http://linked.open...vai/riv/dodaniDat	2013
http://linked.open...aciTvurceVysledku	Martásek, Pavel
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	Všeobecná fakultní nemocnice v Praze / (nerozlišená součást)
http://linked.open...dnocenehoVysledku	142755
http://linked.open...ai/riv/idVysledku	RIV/00064165:_____/12:11398
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Neuronal nitric oxide synthase; Enzyme inhibitors; Intramolecular hydrogen bond; escherichia-coli; monocationic inhibitors; selective inhibitors; drug discovery; cerebral-palsy; active-site; disease; model; analogs; design (en)
http://linked.open.../riv/klicoveSlovo	escherichia-coli analogs active-site Enzyme inhibitors Intramolecular hydrogen bond Neuronal nitric oxide synthase cerebral-palsy drug discovery monocationic inhibitors design disease model selective inhibitors
http://linked.open...odStatuVydavatele	GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV	[3CD84A7D5264]
http://linked.open...i/riv/nazevZdroje	Bioorganic & Medicinal Chemistry
http://linked.open...in/vavai/riv/obor	CE
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	10 (xsd:int)
http://linked.open...UplatneniVysledku	2012
http://linked.open...v/svazekPeriodika	20
http://linked.open...iv/tvurceVysledku	Martásek, Pavel Labby, KJ Mataka, J. Ji, H. T. Kraus, JM Li, HY Poulos, TL Roman, LJ Silverman, RB Xue, FT
http://linked.open...ain/vavai/riv/wos	000301379300027
http://linked.open...n/vavai/riv/zamer	Neuropsychiatrické aspekty neurodegenerativních onemocnění
issn	0968-0896
number of pages	9 (xsd:int)
is http://linked.open...avai/riv/vysledek of	Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase

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