Biophysical characterisation of adducts formed between anticancer metallodrugs and selected proteins: new insights from X-ray diffraction and mass spectrometry studies.
There is considerable interest today for the reactions of anticancer metallodrugs with proteins as these interactions might feature processes that are crucial for the biodistribution, the toxicity and even the mechanism of action of this important group of anticancer agents. We survey here the results of research activities carried out in our "Laboratory of Metals in Medicine" (Department of Chemistry, University of Florence) during the last three years, concerning the molecular characterisation of adducts formed between platinum, ruthenium and gold metallodrugs and a few model proteins. Valuable structural and functional information on these adducts could be derived from several biophysical studies mainly relying on the application of X-ray diffraction and ESI MS techniques. The value and the limitations of both approaches are outlined through a number of examples. Remarkably, the structural and functional information achieved on the respective metallodrug-protein adducts allowed us to identify some general trends in the reactivity of anticancer metallodrugs with protein targets.
Casini
Angela
A
Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze, Italy. angela.casini@unifi.it
Guerri
Annalisa
A
Gabbiani
Chiara
C
Messori
Luigi
L
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D045304:Cytochromes c / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives / Q000737:chemistry; D017612:Gold Compounds / Q000737:chemistry; D006801:Humans; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D017671:Platinum Compounds / Q000737:chemistry; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry; D017975:Ruthenium Compounds; D021241:Spectrometry, Mass, Electrospray Ionization; D013482:Superoxide Dismutase / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry
D000970:Antineoplastic Agents; D017612:Gold Compounds; D008670:Metals; D009942:Organometallic Compounds; D017671:Platinum Compounds; D011506:Proteins; D017975:Ruthenium Compounds; D025801:Ubiquitin; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D045304:Cytochromes c; D013482:Superoxide Dismutase; D009113:Muramidase; D004121:Dimethyl Sulfoxide