. "G\u00F6tz, M. G." . "RIV/60077344:_____/08:00318080" . . . "9" . . . "Hansell, E." . . "James, K. E." . "Kop\u00E1\u010Dek, Petr" . . "10"^^ . "[BABA99E7DF77]" . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . "P(GA206/06/0865), P(LC06009), Z(AV0Z60220518)" . "Aza-peptidy Michael Acceptors. Nov\u00E1 t\u0159\u00EDda \u00FA\u010Dinn\u00FDch a selektivn\u00EDch inhibitor\u016F asparaginylov\u00FDch peptid\u00E1z (legumain\u016F) z evolu\u010Dn\u011B vzd\u00E1len\u00FDch patogen\u016F"@cs . . . "Aza-peptidy tzv. Michael acceptors s obecnou chemickou strukturou Cbz-Ala-Ala-AAsn-trans-CH CHCOR jsou novou t\u0159\u00EDdou inhibitor\u016F specifick\u00FDch pro asparaginylov\u00E9 peptid\u00E1zy (AE, legumainy). Screening vztah\u016F mezi jejich struktorou a aktivitou (SARs) zahrnoval 31 aza-peptid\u016F Michael acceptors a AE ze t\u0159\u00ED parazit\u016F Trichomonas vaginalis, Ixodes ricinus, and Schistosoma mansoni. I kdy\u017E se jedn\u00E1 o evolu\u010Dn\u011B vzd\u00E1len\u00E9 druhy, v\u0161echny t\u0159i enzymy sd\u00EDlely n\u00E1padn\u011B podobn\u00E9 SAR s nejni\u017E\u0161\u00EDmi IC50 hodnotami zasahuj\u00EDc\u00EDmi do pikomolarn\u00EDch koncentrac\u00ED. V\u00FDsledky ukazuj\u00ED na evolu\u010Dn\u00ED rezervovanost v topografii %22prime side%22 aktivn\u00EDho centra AE. SAR tak\u00E9 odhalily \u017Ee estery v P1 pozici jsou v\u00EDce \u00FA\u010Dinn\u00E9 ne\u017E disubstituovan\u00E9 amidy a \u017Ee monosubstituovan\u00E9 amidy a alkylov\u00E9 deriv\u00E1ty v t\u00E9to pozici vedou k mal\u00E9 nebo \u017E\u00E1dn\u00E9 inhibici. Preferovan\u00FDmi P1 zbytky jsou aromatick\u00E9 substituenty. Michael acceptors reaguj\u00ED s thioly, co\u017E nazna\u010Duje mechanismus inhibice aktivn\u00EDho cysteinu AE."@cs . . "Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens"@en . "Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens" . . "51" . "Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens" . . . "McKerrow, J. H." . "Sojka, Daniel" . "Aza-peptidy Michael Acceptors. Nov\u00E1 t\u0159\u00EDda \u00FA\u010Dinn\u00FDch a selektivn\u00EDch inhibitor\u016F asparaginylov\u00FDch peptid\u00E1z (legumain\u016F) z evolu\u010Dn\u011B vzd\u00E1len\u00FDch patogen\u016F"@cs . "Journal of Medicinal Chemistry" . . "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\u2013activity 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." . "legumain; IrAE; aza-peptide Michael acceptors"@en . "000255500000027" . . . "17"^^ . . "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\u2013activity 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 . "Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens"@en . "Dvo\u0159\u00E1k, J." . "Seshaadri, A." . "0022-2623" . "Caffrey, C. R." . "RIV/60077344:_____/08:00318080!RIV09-GA0-60077344" . "2"^^ . . . "Powers, J. C." . "357514" .