Bicyclic peptide inhibitor reveals large contact interface with a protease target.
ACS Chem Biol
; 7(5): 817-21, 2012 May 18.
Article
em En
| MEDLINE
| ID: mdl-22304751
ABSTRACT
From a large combinatorial library of chemically constrained bicyclic peptides we isolated a selective and potent (K(i) = 53 nM) inhibitor of human urokinase-type plasminogen activator (uPA) and crystallized the complex. This revealed an extended structure of the peptide with both peptide loops engaging the target to form a large interaction surface of 701 Å(2) with multiple hydrogen bonds and complementary charge interactions, explaining the high affinity and specificity of the inhibitor. The interface resembles that between two proteins and suggests that these constrained peptides have the potential to act as small protein mimics.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Compostos Bicíclicos com Pontes
/
Ativador de Plasminogênio Tipo Uroquinase
Limite:
Humans
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
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