In:
bchm, Walter de Gruyter GmbH, Vol. 390, No. 11 ( 2009-11-01), p. 1205-1212
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.
Type of Medium:
Online Resource
ISSN:
1437-4315
,
1431-6730
Language:
English
Publisher:
Walter de Gruyter GmbH
Publication Date:
2009
detail.hit.zdb_id:
1466062-3
SSG:
12
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