Cyclic, Linear, Cycloretro-Isomer, and Cycloretro-Inverso Peptides Derived from the C-Terminal Sequence of Bradykinin as Substrates or Inhibitors of Serine and Cysteine Proteases

Cyclic, Linear, Cycloretro-Isomer, and Cycloretro-Inverso Peptides Derived from the C-Terminal Sequence of Bradykinin as Substrates or Inhibitors of Serine and Cysteine Proteases

Autor Lima, Aurelio Resende Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo We investigated the inhibition of trypsin, human tissue (hK1) and human plasma kallikrein (HuPK), papain, and cathepsin L, B, and X by synthetic cyclic, cycloretro-isomer, cycloretro-inverso, and linear peptides derived from the C-terminal sequence of bradykinin. c(FSPFRG) and Ac-FSPFRG-NH(2) were taken as the references for cyclic and linear peptides, respectively. Longer and more flexible analogs of them with addition of 2, 3, or 4 Gly and cycloretro-isomer and cycloretro-inverso analogs of c(FSPFRG) and c(GGGFSPFRG) were obtained and assayed. the susceptibility to hydrolysis of the peptides to all proteases was also examined. the highest affinities were found for c(FSPFRG) with hK1, Ac-GGFSPFRG-NH(2) with HuPK, and psi (NHCO) c(fspfrG) with cathepsin L. the K(i) values for cathepsin B and X with cyclic peptides were lower than those of linear peptides. the serine proteases hydrolyzed all linear and cyclic peptides, except c(FSPFRG) and c(GFSPFRG). the cysteine proteases hydrolyzed only the linear peptides, which were poor substrates. Although the K(i) values obtained in the current work were in the mu M range, the cyclic and cycloretro-inverso peptides seem to be a promising approach to develop efficient and resistant to hydrolysis inhibitors for the kallikreins and lysosomal cysteine proteases.
Palavra-chave Cathepsin B
cathepsin L
cathepsin X
kallikrein
peptides
trypsin
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Human Frontiers for Science Progress
Número do financiamento Human Frontiers for Science Progress: RG 00043/2000-M
Data de publicação 2004-05-01
Publicado em Protein Journal. New York: Springer, v. 23, n. 4, p. 287-294, 2004.
ISSN 1572-3887 (Sherpa/Romeo, fator de impacto)
Publicador Springer
Extensão 287-294
Fonte http://dx.doi.org/10.1023/B:JOPC.0000027853.93513.34
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000208031900006
Endereço permanente http://repositorio.unifesp.br/handle/11600/27757

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