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

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dc.contributor.authorPimenta, D. C.
dc.contributor.authorMelo, R. L.
dc.contributor.authorCaliendo, G.
dc.contributor.authorSantagada, V
dc.contributor.authorFiorino, F.
dc.contributor.authorSeverino, B.
dc.contributor.authorNucci, G. de
dc.contributor.authorJuliano, L.
dc.contributor.authorJuliano, M. A.
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Naples Federico II
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T12:33:23Z
dc.date.available2016-01-24T12:33:23Z
dc.date.issued2002-05-01
dc.description.abstractWe 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.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy
dc.description.affiliationUniv São Paulo, ICB, Dept Pharmacol, BR-05508900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent853-857
dc.identifierhttp://dx.doi.org/10.1515/BC.2002.091
dc.identifier.citationBiological Chemistry. Berlin: Walter de Gruyter & Co, v. 383, n. 5, p. 853-857, 2002.
dc.identifier.doi10.1515/BC.2002.091
dc.identifier.issn1431-6730
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/26866
dc.identifier.wosWOS:000176382200017
dc.language.isoeng
dc.publisherWalter de Gruyter & Co
dc.relation.ispartofBiological Chemistry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjecthuman tissue kallikreinen
dc.subjectinhibitorsen
dc.subjectkallikreinen
dc.subjectnon-natural amino acidsen
dc.subjectsynthetic peptidesen
dc.titleDesign of inhibitors for human tissue kallikrein using non-natural aromatic and basic amino acidsen
dc.typeinfo:eu-repo/semantics/article
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