Irreversible inhibition of human cathepsins B, L, S and K by hypervalent tellurium compounds

Irreversible inhibition of human cathepsins B, L, S and K by hypervalent tellurium compounds

Author Cunha, Rodrigo L. O. R. Autor UNIFESP Google Scholar
Gouvea, Iuri E. Autor UNIFESP Google Scholar
Feitosa, Geovana P. V. Autor UNIFESP Google Scholar
Alves, Marcio F. M. Autor UNIFESP Google Scholar
Broemme, Dieter Google Scholar
Comasseto, Joao V. Google Scholar
Tersariol, Ivarne L. S. Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do ABC (UFABC)
Univ British Columbia
Universidade de São Paulo (USP)
Univ Mogi das Cruzes
Abstract The inhibition of human cysteine cathepsins B, L, S and K was evaluated by a set of hypervalent tellurium compounds (telluranes) comprising both organic and inorganic derivatives. All telluranes studied showed a time-and concentration-dependent irreversible inhibition of the cathepsins, and their second-order inactivation rate constants were determined. the organic derivatives were potent inhibitors of the cathepsins and clear specificities were detected, which were parallel to their known substrate specificities. in all cases, the activity of the tellurane-inhibited cathepsins was recovered by treatment of the inactivated enzymes with reducing agents. the maximum stoichiometry of the reaction between cysteine residues and telluranes were also determined. the presented data indicate that it is possible to design organic compounds with a tellurium(IV) moiety as a novel warhead that covalently modifies the catalytic cysteine, and which also form strong interactions with subsites of cathepsins B, L, S and K, resulting in more specific inhibition.
Keywords cysteine protease
inhibitors
peptidase
protease
telluranes
Language English
Date 2009-11-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 390, n. 11, p. 1205-1212, 2009.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 1205-1212
Origin http://dx.doi.org/10.1515/BC.2009.125
Access rights Closed access
Type Article
Web of Science ID WOS:000270513600015
URI http://repositorio.unifesp.br/handle/11600/31947

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