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| rdf:type
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| Description
| - Aza-peptidy tzv. Michael acceptors s obecnou chemickou strukturou Cbz-Ala-Ala-AAsn-trans-CH CHCOR jsou novou třídou inhibitorů specifických pro asparaginylové peptidázy (AE, legumainy). Screening vztahů mezi jejich struktorou a aktivitou (SARs) zahrnoval 31 aza-peptidů Michael acceptors a AE ze tří parazitů Trichomonas vaginalis, Ixodes ricinus, and Schistosoma mansoni. I když se jedná o evolučně vzdálené druhy, všechny tři enzymy sdílely nápadně podobné SAR s nejnižšími IC50 hodnotami zasahujícími do pikomolarních koncentrací. Výsledky ukazují na evoluční rezervovanost v topografii %22prime side%22 aktivního centra AE. SAR také odhalily že estery v P1 pozici jsou více účinné než disubstituované amidy a že monosubstituované amidy a alkylové deriváty v této pozici vedou k malé nebo žádné inhibici. Preferovanými P1 zbytky jsou aromatické substituenty. Michael acceptors reagují s thioly, což naznačuje mechanismus inhibice aktivního cysteinu AE. (cs)
- Aza-peptide Michael acceptors with the general structure of Cbz-Ala-Ala-AAsn-trans-CH CHCOR are a new class of inhibitors specific for the asparaginyl endopeptidases (AE) (legumains). Structure–activity relationships (SARs) were characterized for a set of 31 aza-peptide Michael acceptors with AEs derived from three parasites: Trichomonas vaginalis, Ixodes ricinus, and Schistosoma mansoni. Despite arising from phylogenetically disparate organisms, all three AEs shared a remarkably similar SAR with lowest IC50 values extending into the picomolar range. The results suggest an evolutionary constraint on the topography of the prime side of the active site. SAR also revealed that esters in the P1 position are more potent than disubstituted amides and that monosubstituted amides and alkyl derivatives show little or no inhibition. The preferred P1 residues have aromatic substituents. Michael acceptors react with thiols what provides an insight into the mechanism of their inhibition.
- Aza-peptide Michael acceptors with the general structure of Cbz-Ala-Ala-AAsn-trans-CH CHCOR are a new class of inhibitors specific for the asparaginyl endopeptidases (AE) (legumains). Structure–activity relationships (SARs) were characterized for a set of 31 aza-peptide Michael acceptors with AEs derived from three parasites: Trichomonas vaginalis, Ixodes ricinus, and Schistosoma mansoni. Despite arising from phylogenetically disparate organisms, all three AEs shared a remarkably similar SAR with lowest IC50 values extending into the picomolar range. The results suggest an evolutionary constraint on the topography of the prime side of the active site. SAR also revealed that esters in the P1 position are more potent than disubstituted amides and that monosubstituted amides and alkyl derivatives show little or no inhibition. The preferred P1 residues have aromatic substituents. Michael acceptors react with thiols what provides an insight into the mechanism of their inhibition. (en)
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| Title
| - Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens
- Aza-peptidy Michael Acceptors. Nová třída účinných a selektivních inhibitorů asparaginylových peptidáz (legumainů) z evolučně vzdálených patogenů (cs)
- Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens (en)
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| skos:prefLabel
| - Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens
- Aza-peptidy Michael Acceptors. Nová třída účinných a selektivních inhibitorů asparaginylových peptidáz (legumainů) z evolučně vzdálených patogenů (cs)
- Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens (en)
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| skos:notation
| - RIV/60077344:_____/08:00318080!RIV09-GA0-60077344
|
| http://linked.open...avai/riv/aktivita
| |
| http://linked.open...avai/riv/aktivity
| - P(GA206/06/0865), P(LC06009), Z(AV0Z60220518)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
| |
| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
| |
| http://linked.open...ai/riv/idVysledku
| - RIV/60077344:_____/08:00318080
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| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - legumain; IrAE; aza-peptide Michael acceptors (en)
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| http://linked.open.../riv/klicoveSlovo
| |
| http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
| - Journal of Medicinal Chemistry
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| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
| |
| http://linked.open...iv/tvurceVysledku
| - Dvořák, J.
- Kopáček, Petr
- Sojka, Daniel
- Caffrey, C. R.
- McKerrow, J. H.
- Götz, M. G.
- Hansell, E.
- James, K. E.
- Powers, J. C.
- Seshaadri, A.
|
| http://linked.open...ain/vavai/riv/wos
| |
| http://linked.open...n/vavai/riv/zamer
| |
| issn
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| number of pages
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| is http://linked.open...avai/riv/vysledek
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