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Eur J Pharmacol ; 666(1-3): 53-60, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21658384

RESUMEN

Chronic wounds are the result of excessive amounts of tissue destructive proteases such as human neutrophil elastase (HNE). The high levels of this enzyme found on those types of wounds inactivate the endogenous inhibitor barrier thus, the search for new HNE inhibitors is required. This work presents two new HNE inhibitor peptides, which were synthesized based on the reactive-site loop of the Bowman-Birk inhibitor protein. The results obtained indicated that these new peptides are competitive inhibitors for HNE and, the inhibitory activity can be modulated by modifications introduced at the N- and C-terminal of the peptides. Furthermore, these peptides were also able to inhibit elastase from a human wound exudate while showing no cytotoxicity against human skin fibroblasts in vitro, greatly supporting their potential application in chronic wound treatment.


Asunto(s)
Elastasa de Leucocito/antagonistas & inhibidores , Péptidos/farmacología , Proteínas Inhibidoras de Proteinasas Secretoras/farmacología , Secuencia de Aminoácidos , Animales , Dominio Catalítico , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroínas/metabolismo , Humanos , Concentración 50 Inhibidora , Cinética , Elastasa de Leucocito/química , Elastasa de Leucocito/metabolismo , Ensayo de Materiales , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Péptidos/química , Péptidos/metabolismo , Péptidos/toxicidad , Proteínas Inhibidoras de Proteinasas Secretoras/química , Proteínas Inhibidoras de Proteinasas Secretoras/metabolismo , Proteínas Inhibidoras de Proteinasas Secretoras/toxicidad , Especificidad por Sustrato , Inhibidor de la Tripsina de Soja de Bowman-Birk/química
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