Metallodrugs interactions

Ravera, M., Bagni, G., Mascini, M., Osella, D. DNA-metallodrugs interactions signaled by electrochemical biosensors An overview. Bioinorg. Chem. Appl, Article ID 91078, 1-11 (2007)... 

Casini A, Gabbiani C, Michelucci E, Pieraccini G, Moneti G, Dyson PJ, Messori L (2009) Exploring metallodrug-protein interactions by mass spectrometry comparisons between platinum coordination complexes and an organometallic ruthenium compound. J Biol Inorg Chem 14 761-770... 

Timerbaev AR, Hartinger CG, Aleksenko SS, Keppler BK (2006) Interactions of antitumor metallodrugs with serum proteins advances in characterization using modem analytical methodology. Chem Rev 106 2224-2248... 

GroessI, M., Tsybin, Y.O., Hartinger, C.G., Keppler, B.K., Dyson, P.J. Ruthenium versus platinum interactions of anticancer metallodrugs with duplex oligonucleotides characterized by electrospray ionization mass spectrometry. J. Biol. Inorg. Chem. 15, 677-688 (2010)... 

Szpunar, J., Makarov, A., Lobinski, R., Pieper, T., Keppler, B. K. Investigation of metallodrug-protein interactions by size-exclusion chromatography coupled with inductively coupled plasma mass spectrometry (ICP-MS). Anal Chim Acta 1999, 387, 135-144. 

Hadjiliadis, N. and Sletten, E. (eds) (2009) Metal Complex — DNA Interactions, Wiley-Blackwell, Oxford, UK. Overviews metal-DNA interactions and mechanisms, metallodrugs and toxicity includes a deep coverage of cisplatin. 

The hydrolysis of metallodrugs is often the key step in their activation, but the timescale is extremely variable, ranging from tenths of a second for titanocene dichloride, to hours for cisplatin, to days for carboplatin. We found on SPE that the interaction of cisplatin with DNA increases with the solution ageing time, especially at low concentrations of chlorides [50]. Each complex was therefore preactivated for 60 minutes before testing interaction with DNA, in order to permit the transformation into the active aqua species, for the complexes needing this incubation time, and to compare the behavior at the same solntion ageing time, for the complexes with a different rate of hydrolysis. 

Albumin is one of the most abundant proteins in plasma ( 0.63 mM) and it is reasonable to assume that any injected metallodrug will present certain interactions with this macromolecule, which could largely determine its bioavailability and toxicology [42]. A comprehensive study of the reactions of the N-labeled cisplatin with intact and chemically modified recombinant human albumin (rHA) as well as human serum album (HSA) has been performed by ID H and [ H, Nj 2D HSQC NMR spectroscopy [53]. Recombinant albumin is similar to serum albumin but has a higher thiol content ( 0.9 -SH per rHA and only 0.4-SH per HSA) and is structurally more homogeneous. NMR studies showed that the major sulfur-containing binding site involves Met in the form of an S, N chelate but not Cys-34, which is commonly believed to be the major platination site of HSA (Scheme 5.4) [73]. 

With the exponential explosion of research into anticancer metallodrugs some original entities of Ru act via a structural role for the metal, which would give its shape to the compound and would favor noncovalent interactions with the target, as for example the organometallic 10 (Fig. 42.3), an excellent inhibitor of certain protein kinases developed by Meggers [27, 82],... 

The in vitro interactions of the cysteine-rich intracellular protein Zn7-metal-lothionein with cisplatin and transplatin and the histidine-rich proteins Hpni32,i33 HspA with a bismuth antiulcer compound were investigated, respectively. These kinds of interactions may play a crucial role in the metabolism of various metallodrugs. Notably, drug binding to plasma proteins has a strong influence on their biodistribution, biotransformation, and pharmacokinetics, and therefore merits further characterizations. 

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