About: Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

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About: Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases) Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CHdCHCOR are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and 8 aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P1 position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs. Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CHdCHCOR are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and 8 aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P1 position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs. (en)
Title	Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases) Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases) (en)
skos:prefLabel	Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases) Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases) (en)
skos:notation	RIV/60077344:_____/09:00335281!RIV10-MSM-60077344
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(GA206/06/0865), P(LC06009), Z(AV0Z60220518)
http://linked.open...iv/cisloPeriodika	22
http://linked.open...vai/riv/dodaniDat	2010
http://linked.open...aciTvurceVysledku	Kopáček, Petr Sojka, Daniel
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	Biologické centrum AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	304593
http://linked.open...ai/riv/idVysledku	RIV/60077344:_____/09:00335281
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	legumain; IrAE; aza-peptide Michael acceptors (en)
http://linked.open.../riv/klicoveSlovo	IrAE aza-peptide Michael acceptors legumain
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[4C0441998B4E]
http://linked.open...i/riv/nazevZdroje	Journal of Medicinal Chemistry
http://linked.open...in/vavai/riv/obor	EC
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	11 (xsd:int)
http://linked.open...vavai/riv/projekt	Centre for molecular ecology of vectors and pathogens Peptidases in the gut of the hard tick Ixodes ricinus: characterization and potential for vector-control
http://linked.open...UplatneniVysledku	2009
http://linked.open...v/svazekPeriodika	52
http://linked.open...iv/tvurceVysledku	Dvořák, J. Kopáček, Petr Sojka, Daniel Caffrey, C. R. McKerrow, J. H. Hansell, E. Powers, J. C. Brouner, M. Fagan, C. Muindi, F. Ovat, A.
http://linked.open...ain/vavai/riv/wos	000271825600024
http://linked.open...n/vavai/riv/zamer	Parazitismus a parazito-hostitelské vztahy na organismální, buněčné a molekulové úrovni
issn	0022-2623
number of pages	19 (xsd:int)

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