Artigo
Plasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitor
Fecha
2010-05-01Registro en:
Biological Chemistry. Berlin: Walter de Gruyter Gmbh, v. 391, n. 5, p. 561-570, 2010.
1431-6730
10.1515/BC.2010.049
WOS:000277536500010
Autor
Coppini, Larissa Pereira [UNIFESP]
Barros, Nilana M. T. [UNIFESP]
Oliveira, Marcela [UNIFESP]
Hirata, Izaura Y. [UNIFESP]
Alves, Marcio F. M. [UNIFESP]
Paschoalin, Thaysa [UNIFESP]
Assis, Diego M. [UNIFESP]
Juliano, Maria A. [UNIFESP]
Puzer, Luciano
Broemme, Dieter
Carmona, Adriana K. [UNIFESP]
Institución
Resumen
Plasminogen is a glycoprotein implicated in angiogenesis and fibrin clot degradation associated with the release of angiostatin and plasmin activation, respectively We have recently reported that cathepsin V. but not cathepsins L. B, and K. can release angiostatin-like fragments from plasminogen. Here, we extended the investigation to cathepsin S which has been implicated in angiogenesis and tumor cell proliferation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of plasminogen hydrolysis by cathepsin S revealed generation of two fragments (60 and 38 kDa). Amino-terminal sequencing indicated that cleavage occurs at the Leu469-Leu470 peptide bond. in contrast to cathepsin V, which possesses antiangiogenic activity, cathepsin S plasminogen cleavage products were not capable of inhibiting angiogenesis on endothelial cells. Moreover, we explored the different selectivities presented by cathepsins V and S towards plasminogen and synthesized fluorescence resonance energy transfer peptides encompassing the hydrolyzed peptide bonds by both enzymes. the peptide Abz-VLFEKKQ-EDDnp (Abz=ortho-aminobenzoic acid; EDDnp=N-[2,4-dinitrophenyl]ethylenediamine), hydrolyzed by cathepsin V at the Phe-Glu bond. is a selective substrate for the enzyme when compared with cathepsins B. L, and S, whereas Abz-VLFEKKVYLQ-EDDnp is an efficient cathepsin L inhibitor. the demonstrated importance of the S-3'-P-3' interaction indicates the significance of the extended subsites for enzyme specificity and affinity.
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
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
Lima, Aurelio Resende [UNIFESP]; Juliano, Luiz [UNIFESP]; Juliano, Maria Aparecida [UNIFESP] (Springer, 2004-05-01)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 ... -
Synthesis and hydrolysis by cathepsin B of fluorogenic substrates with the general structure benzoyl-X-ARG-MCA containing non-natural basic amino acids at position X
Melo, Robson L [UNIFESP]; Pozzo, Roseli C Barbosa [UNIFESP]; Alves, Lira C [UNIFESP]; Perissutti, Elisa; Caliendo, Giuseppe; Santagada, Vincenzo; Juliano, Luiz [UNIFESP]; Juliano, Maria A. [UNIFESP] (Elsevier B.V., 2001-05-05)We synthesized one series of fluorogenic substrates for cathepsin B derived from the peptide Bz-F-R-MCA (Bz = benzoyl, MCA = 7-methyl-coumarin amide) substituting Phe at the P(2) position by non-natural basic amino acids ... -
Palladacycle (BPC) antitumour activity against resistant and metastatic cell lines: the relationship with cytosolic calcium mobilisation and cathepsin B activity
Bechara, Alexandre [UNIFESP]; Barbosa, Christiano Marcello Vaz [UNIFESP]; Paredes-Gamero, Edgar Julian [UNIFESP]; Garcia, Daniel Moreno [UNIFESP]; Silva, Luis S. [UNIFESP]; Matsuo, Alisson Leonardo [UNIFESP]; Nascimento, Fábio Dupart; Rodrigues, Elaine Guadelupe [UNIFESP]; Caires, Antonio Carlos Favero; Smaili, Soraya Soubhi [UNIFESP]; Bincoletto, Claudia [UNIFESP] (Elsevier B.V., 2014-05-22)The search for new compounds that induce p53-independent apoptosis is the focus of many studies in cancer biology because these compounds could be more specific and would overcome chemotherapy resistance. in this study, ...