Please use this identifier to cite or link to this item:
|Title:||Design of inhibitors for human tissue kallikrein using non-natural aromatic and basic amino acids|
|Authors:||Pimenta, D. C.|
Melo, R. L.
Nucci, G. de
Juliano, M. A.
Universidade Federal de São Paulo (UNIFESP)
Univ Naples Federico II
Universidade de São Paulo (USP)
|Keywords:||human tissue kallikrein|
non-natural amino acids
|Publisher:||Walter de Gruyter & Co|
|Citation:||Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 383, n. 5, p. 853-857, 2002.|
|Abstract:||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.|
|Appears in Collections:||Em verificação - Geral|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.