Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/32535
Title: Plasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitor
Authors: 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]
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Triangulo Mineiro
Univ British Columbia
Keywords: angiostatin
cathepsin L
cathepsin S
cathepsin V
fluorescence resonance energy transfer peptides
plasminogen
Issue Date: 1-May-2010
Publisher: Walter de Gruyter Gmbh
Citation: Biological Chemistry. Berlin: Walter de Gruyter Gmbh, v. 391, n. 5, p. 561-570, 2010.
Abstract: 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.
URI: http://repositorio.unifesp.br/handle/11600/32535
ISSN: 1431-6730
Other Identifiers: http://dx.doi.org/10.1515/BC.2010.049
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