Properties of the reaction of cis-dichlorodiammineplatinum(II) with metallothionein.

Metal-binding mechanisms in metallothioneins

“…23,25 Metalation studies of MT involved either the binding of metals to apo-MT or the substitution of metalated-MT with a metal with a stronger binding constant. 24,26,27 Demetalation studies of metalated-MT used either a chelator to remove the metals or an electrophile to displace the metals. [28][29][30][31] During the 1990's, the kinetic reactions of MT were studied using optical spectroscopy; with most studies concluding that the reaction was biphasic and that the kinetic data could be fitted using two pseudo-first order mechanisms.…”

“…27-33 Further, one paper reported that there was an induction step in the reaction before the biphasic reaction. 27 The biphasic mechanism was interpreted as due to the differential reactivity of the clusters to the different metals, chelaters and electrophiles used. A selective summary comparing the cluster reactivity can be found in the paper by Munoz et al 32 In 2002, Petering et al studied metalation of apo-MT with Cd 2+ , Zn 2+ , and Co 2+ .…”

“…24 From these kinetic studies, a few key conclusions were reported. Firstly, the metalation reaction was potentially cooperative, 27 yet intermediates likely existed. 27, 29 Later, Shaw et al stated that the reaction mechanism could not be cooperative for the alkylation of MT 29 nonetheless, during this time period no conclusive statement was made that the metalation reaction mechanism was noncooperative.…”

Reactivity of an antimetastatic organometallic ruthenium compound with metallothionein-2: relevance to the mechanism of action

“…However, these metals can be displaced by other metal ions in vivo that have a higher affinity for thiolates such as Cd(II), Hg(II), and Pt(II), and the molecular mechanisms of the Pt(II) interactions with MT-1/-2 have been the subject of numerous studies. [33][34][35][36] As far as we are aware, studies on the interaction of MTs with ruthenium compounds are lacking, despite the growing interest in ruthenium anticancer drugs and their ability to function in platinum-resistant tumours. Herein, we describe the use of electrospray ionisation mass spectrometry (ESI MS) to probe the interactions of RAPTA-C with rabbit MT-2, using cisplatin as a reference compound.…”

Nitric oxide induces Zn2+ release from metallothionein by destroying zinc‒sulphur clusters without concomitant formation of S-nitrosothiol

“…Other isoforms such as MT3 and MT4 are reported to be expressed in the brain [15,16] and in mouse tissues containing stratified squamous epithelial cells [17], respectively. The elucidation of the possible role of MT in the cellular response to NO is of particular importance, as MT has been shown to be involved in protecting cells from a variety of toxic substances including metal ions [18][19][20]. Also, MT has been postulated to play a role in scavenging hydroxyl and superoxide radicals and the appropriate reaction processes have been studied [21,22].…”