Engineered cystine knot miniproteins as potent inhibitors of human mast cell tryptase beta.
J Mol Biol
; 395(1): 167-75, 2010 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-19852971
ABSTRACT
Here we report the design, chemical and recombinant synthesis, and functional properties of a series of novel inhibitors of human mast cell tryptase beta, a protease of considerable interest as a therapeutic target for the treatment of allergic asthma and inflammatory disorders. These inhibitors are derived from a linear variant of the cyclic cystine knot miniprotein MCoTI-II, originally isolated from the seeds of Momordica cochinchinensis. A synthetic cyclic miniprotein that bears additional positive charge in the loop connecting the N- and C-termini inhibits all monomers of the tryptase beta tetramer with an overall equilibrium dissociation constant K(i) of 1 nM and thus is one of the most potent proteinaceous inhibitors of tryptase beta described to date. These cystine knot miniproteins may therefore become valuable scaffolds for the design of a new generation of tryptase inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Engenharia de Proteínas
/
Ciclotídeos
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Motivos Nó de Cisteína
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Triptases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Alemanha