Pre-association of polynuclear platinum anticancer agents on a protein, human serum albumin. Implications for drug design.
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.
Montero
Eva I
EI
Department of Chemistry, Virginia Commonwealth University, 1001 W. Main St., Richmond, VA 23284-2006, USA.
Benedetti
Brad T
BT
Mangrum
John B
JB
Oehlsen
Michael J
MJ
Qu
Yun
Y
Farrell
Nicholas P
NP
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
D000970:Antineoplastic Agents; D012709:Serum Albumin; D010984:Platinum