Design and synthesis of irreversible inhibitors of foot-and-mouth disease virus 3C protease.
Bioorg Med Chem Lett
; 24(2): 490-4, 2014 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-24374278
ABSTRACT
Foot-and-mouth disease virus (FMDV) causes a highly infectious and economically devastating disease of livestock. The FMDV genome is translated as a single polypeptide precursor that is cleaved into functional proteins predominantly by the highly conserved viral 3C protease, making this enzyme an attractive target for antiviral drugs. A peptide corresponding to an optimal substrate has been modified at the C-terminus, by the addition of a warhead, to produce irreversible inhibitors that react as Michael acceptors with the enzyme active site. Further investigation highlighted key structural determinants for inhibition, with a positively charged P2 being particularly important for potency.
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Proteínas Virais
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Cisteína Endopeptidases
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Desenho de Fármacos
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Vírus da Febre Aftosa
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article