Design of inhibitors for human tissue kallikrein using non-natural aromatic and basic amino acids

Design of inhibitors for human tissue kallikrein using non-natural aromatic and basic amino acids

Autor Pimenta, D. C. Google Scholar
Melo, R. L. Google Scholar
Caliendo, G. Google Scholar
Santagada, V Google Scholar
Fiorino, F. Google Scholar
Severino, B. Google Scholar
Nucci, G. de Google Scholar
Juliano, L. Google Scholar
Juliano, M. A. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Naples Federico II
Universidade de São Paulo (USP)
Resumo We explored the unique substrate specificity of the primary S1 subsite of human urinary kallikrein (hK1), which accepts both Phe or Arg synthesizing and assaying peptides derived from PhenylacetylPheSer ArgEDDnp, a previously described inhibitor with analgesic and antiinflammatory activities [Emim et al., Br. J. Pharmacol. 130 (2000), 1099 1107]. Phe was substituted by amino acids containing larger aliphatic or aromatic side chains as well as by nonnatural basic amino acids, which were designed to combine a large hydrophobic and/or aromatic group with a positivelycharged group at their side chains. in general, all peptides with basic amino acids represented better inhibitors than those with hydrophobic amino acids. Furthermore, the S1 subsite specificity proved to be much more selective than the mere distinction between Phe and Arg, for minor differences in the side chains of the nonnatural amino acids resulted in major differences in the K-i values. Finally, we present a series of peptides that were assayed as competitive inhibitors for human tissue kallikrein that may lead to the development of novel peptides, which are both more potent and selective.
Assunto human tissue kallikrein
non-natural amino acids
synthetic peptides
Idioma Inglês
Data 2002-05-01
Publicado em Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 383, n. 5, p. 853-857, 2002.
ISSN 1431-6730 (Sherpa/Romeo, fator de impacto)
Editor Walter de Gruyter & Co
Extensão 853-857
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000176382200017

Mostrar registro completo

Arquivos deste item

Arquivos Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item aparece na(s) seguinte(s) coleção(s)