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Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry



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Dalton Trans., 2007, 4938 - 4942, DOI: 10.1039/b708433c

Pre-association of polynuclear platinum anticancer agents on a protein, human serum albumin. Implications for drug design

Eva I. Montero, Brad T. Benedetti, John B. Mangrum, Michael J. Oehlsen, Yun Qu and Nicholas P. Farrell

The interactions of polynuclear platinum complexes with human serum albumin were studied. The compounds examined were the non-covalent analogs of the trinuclear BBR3464 as well as the dinuclear spermidine-bridged compounds differing in only the presence or absence of a central –NH2–+ (BBR3571 and analogs). Thus, closely-related compounds could be compared. Evidence for pre-association, presumably through electrostatic and hydrogen-bonding, was obtained from fluorescence and circular dichroism spectroscopy and Electrospray Ionization Mass Spectrometry (ESI-MS). In the case of those compounds containing Pt-Cl bonds, further reaction took place presumably through displacement by sulfur nucleophiles. The implications for protein pre-association and plasma stability of polynuclear platinum compounds are discussed.

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