A group of mixed-ligand Pt(II) complexes bearing acetylacetonate and sulphur ligands were recently developed in the University of Lecce as a new class of prospective anticancer agents that manifested promising pharma-cological properties in preliminary in vitro and in vivo tests. Though modelled on the basis of cisplatin, these Pt(II) complexes turned out to exhibit a profoundly distinct mode of action as they were found to act mainly on non-genomic targets rather than on DNA. Accordingly, we have explored here their reactions with two representative model proteins through an established ESI-MS procedure with the aim to describe their general interaction mechanism with protein targets. A pronounced reactivity with the tested proteins was indeed documented; the nature of the resulting metallodrug-protein interactions could be characterised in depth in the various cases. Preferential binding to protein targets compared to DNA is supported by independent ICP-OES measurements. The implications of these findings are discussed.
ESI-MS studies of the reactions of novel platinum(II) complexes containing O,O'-chelated acetylacetonate and sulfur ligands with selected model proteins / Marzo, Tiziano; De Pascali, Sandra A; Gabbiani, Chiara; Fanizzi, Francesco P; Messori, Luigi; Pratesi, Alessandro. - In: BIOMETALS. - ISSN 0966-0844. - ELETTRONICO. - 30:(2017), pp. 609-614-614. [10.1007/s10534-017-0031-0]
ESI-MS studies of the reactions of novel platinum(II) complexes containing O,O'-chelated acetylacetonate and sulfur ligands with selected model proteins
MARZO, TIZIANO;FANIZZI, FRANCESCO PAOLO;MESSORI, LUIGI;PRATESI, ALESSANDRO
2017
Abstract
A group of mixed-ligand Pt(II) complexes bearing acetylacetonate and sulphur ligands were recently developed in the University of Lecce as a new class of prospective anticancer agents that manifested promising pharma-cological properties in preliminary in vitro and in vivo tests. Though modelled on the basis of cisplatin, these Pt(II) complexes turned out to exhibit a profoundly distinct mode of action as they were found to act mainly on non-genomic targets rather than on DNA. Accordingly, we have explored here their reactions with two representative model proteins through an established ESI-MS procedure with the aim to describe their general interaction mechanism with protein targets. A pronounced reactivity with the tested proteins was indeed documented; the nature of the resulting metallodrug-protein interactions could be characterised in depth in the various cases. Preferential binding to protein targets compared to DNA is supported by independent ICP-OES measurements. The implications of these findings are discussed.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.