The formation of amorphous protein aggregates containing human superoxide dismutase (hSOD1) is thought to be involved in amyotrophic lateral sclerosis onset. cis-Platin inhibits the oligomerization of apo hSOD1, but its toxicity precludes any possible use in therapy. Herein, we propose a less toxic platinum complex, namely oxa/cis-platin, as hSOD1 antiaggregation lead compound. Oxa/cis-platin is able to interact with hSOD1 in the disulfide oxidized apo form by binding cysteine 111 (Cys111). The mild neurotoxic phenomena induced in vitro and in vivo by oxa/cis-platin can be successfully reverted by using lypoyl derivatives, which do not interfere with the antiaggregation properties of the platin derivative.

Interaction of Half Oxa-/Half cis-Platin Complex with Human Superoxide Dismutase and Induced Reduction of Neurotoxicity / Francesca Cantini, Vito Calderone, Lorenzo Di Cesare Mannelli, Magdalena Korsak, Leonardo Gonnelli, Oscar Francesconi, Carla Ghelardini, Lucia Banci, and Cristina Nativi. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - STAMPA. - 9:(2018), pp. 1094-1098. [10.1021/acsmedchemlett.8b00199]

Interaction of Half Oxa-/Half cis-Platin Complex with Human Superoxide Dismutase and Induced Reduction of Neurotoxicity

Francesca Cantini;Vito Calderone;Lorenzo Di Cesare Mannelli;Magdalena Korsak;Leonardo Gonnelli;Oscar Francesconi;Carla Ghelardini;Lucia Banci;
2018

Abstract

The formation of amorphous protein aggregates containing human superoxide dismutase (hSOD1) is thought to be involved in amyotrophic lateral sclerosis onset. cis-Platin inhibits the oligomerization of apo hSOD1, but its toxicity precludes any possible use in therapy. Herein, we propose a less toxic platinum complex, namely oxa/cis-platin, as hSOD1 antiaggregation lead compound. Oxa/cis-platin is able to interact with hSOD1 in the disulfide oxidized apo form by binding cysteine 111 (Cys111). The mild neurotoxic phenomena induced in vitro and in vivo by oxa/cis-platin can be successfully reverted by using lypoyl derivatives, which do not interfere with the antiaggregation properties of the platin derivative.
2018
9
1094
1098
Francesca Cantini, Vito Calderone, Lorenzo Di Cesare Mannelli, Magdalena Korsak, Leonardo Gonnelli, Oscar Francesconi, Carla Ghelardini, Lucia Banci, ...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1137500
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