Počet záznamů: 1
Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)
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SYSNO ASEP 0335281 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases) Tvůrce(i) Ovat, A. (US)
Muindi, F. (US)
Fagan, C. (US)
Brouner, M. (US)
Hansell, E. (US)
Dvořák, J. (US)
Sojka, Daniel (BC-A) RID, ORCID
Kopáček, Petr (BC-A) RID, ORCID
McKerrow, J. H. (US)
Caffrey, C. R. (US)
Powers, J. C. (US)Zdroj.dok. Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623
Roč. 52, č. 22 (2009), s. 7192-7210Poč.str. 19 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova legumain ; IrAE ; aza-peptide Michael acceptors Vědní obor RIV EC - Imunologie CEP GA206/06/0865 GA ČR - Grantová agentura ČR LC06009 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy CEZ AV0Z60220518 - PAU-O, BC-A (2005-2011) UT WOS 000271825600024 DOI 10.1021/jm900849h Anotace 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. Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2010
Počet záznamů: 1