title: Pre-association of polynuclear platinum anticancer agents on a protein, human serum albumin. Implications for drug design.
abstract: 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 -NH(2)-(+) (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.
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, 1001 W. Main St., Richmond, VA 23284-2006, USA.
authors.forename: Eva I
authors.initials: EI
authors.lastname: Montero
authors.forename: Brad T
authors.initials: BT
authors.lastname: Benedetti
authors.forename: John B
authors.initials: JB
authors.lastname: Mangrum
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Oehlsen
authors.forename: Yun
authors.initials: Y
authors.lastname: Qu
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Farrell
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002942:Circular Dichroism; D015195:Drug Design; D010984:Platinum / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D012709:Serum Albumin; D010984:Platinum