Inhibition of cruzipain visualized in a fluorescence quenched solid-phase inhibitor library assay. D-amino acid inhibitors for cruzipain, cathepsin B and cathepsin L

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dc.contributor.author Meldal, M.
dc.contributor.author Svendsen, I
dc.contributor.author Juliano, L.
dc.contributor.author Juliano, M. A.
dc.contributor.author Del Nery, E.
dc.contributor.author Scharfstein, J.
dc.date.accessioned 2016-01-24T12:30:34Z
dc.date.available 2016-01-24T12:30:34Z
dc.date.issued 1998-04-01
dc.identifier http://dx.doi.org/10.1002/(SICI)1099-1387(199804)4:2<83
dc.identifier.citation Journal of Peptide Science. W Sussex: John Wiley & Sons Ltd, v. 4, n. 2, p. 83-91, 1998.
dc.identifier.issn 1075-2617
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/25882
dc.description.abstract A PEGA-resin was derivatized with a 3:1 mixture of hydroymethyl benzoic acid and Fmoc-Lys(Boc)-OH and the fluorogenic substrate Ac-Y(NO2)KLRFSKQK(Abz)-PEGA was assembled on the lysine using the active ester approach. Following esterification of the hydroxymethyl benzoic acid with Fmoc-Val-OH a library XXX-k/r-XXXV containing approximately 200,000 beads was assembled by split synthesis. the resulting 'one bead, two peptides' library was subjected to extensive hydrolysis with cruzipain. One hundred darker beads were isolated and the 14 most persistently dark beads were collected and sequenced. the putative inhibitor peptides and several analogues were synthesized and found to be competitive mu M to nM inhibitors of cruzipain in solution. the inhibitory activity was found to be unspecific to cruzipain when compared with cathepsins B and L and specific when compared with kallikrein. One of the inhibitors was docked into the active site of cathepsin B and was found most probably to bind to the enzyme cavity in an unusual manner, owing to the inserted D-amino acid residue. (C) 1998 European Peptide Society and John Wiley & Sons, Ltd. en
dc.format.extent 83-91
dc.language.iso eng
dc.publisher Wiley-Blackwell
dc.relation.ispartof Journal of Peptide Science
dc.rights Acesso restrito
dc.subject fluorescence quenched assay en
dc.subject inhibitor library en
dc.subject Trypanosoma cruzi en
dc.subject cathepsin B and L inhibitors en
dc.subject parasitic protease inhibition en
dc.title Inhibition of cruzipain visualized in a fluorescence quenched solid-phase inhibitor library assay. D-amino acid inhibitors for cruzipain, cathepsin B and cathepsin L en
dc.type Artigo
dc.rights.license http://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.contributor.institution Carlsberg Lab
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Universidade Federal do Rio de Janeiro (UFRJ)
dc.description.affiliation Carlsberg Lab, Dept Chem, DK-2500 Copenhagen, Denmark
dc.description.affiliation Escola Paulista Med, BR-04023 São Paulo, Brazil
dc.description.affiliation Fed Univ Rio de Janeiro, Mol Immunol Lab, Inst Biofis Carlos Chagas Filho, Rio de Janeiro, Brazil
dc.description.affiliationUnifesp Escola Paulista Med, BR-04023 São Paulo, Brazil
dc.identifier.doi 10.1002/(SICI)1099-1387(199804)4:2<83
dc.description.source Web of Science
dc.identifier.wos WOS:000073108900001



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