Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action
Impacto
Scholar |
Otros documentos de la autoría: Royo Calvo, Santiago; Rodríguez, Santiago; Schirmeister, Tanja; Kesselring, Jochen; Kaiser, Marcel; González, Florenci
Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
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http://dx.doi.org/10.1002/cmdc.201500204 |
Metadatos
Título
Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of ActionAutoría
Fecha de publicación
2015-07-14Editor
WileyISSN
1860-7179Cita bibliográfica
ROYO, Santiago, et al. Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action. ChemMedChem, 2015, vol. 10, no 9, p. 1484-1487.Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201500204/fullPalabras clave / Materias
Resumen
Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened ... [+]
Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened against rhodesain and human cathepsins B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (S,E)-ethyl 5-((S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido)-7-methyl-4-oxooct-2-enoate (6) was the most potent, with an IC50 value of 16.4 nm and kinact/Ki=1.6×106 m−1 s−1 against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition kinetics data, supported by docking studies, suggest a dual mode of action via attack of cysteine thiolate at two reactive positions. [-]
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ChemMedChem, 2015, vol. 10, no 9Derechos de acceso
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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