Platinated oligomers of bovine pancreatic ribonuclease: Structure and stability

• Oligomeric forms of RNase A were obtained in the presence of cisplatin.
• The yield of platinated RNase A oligomers depends on cisplatin/RNase A ratio.
• Platinated RNase A derivatives were characterized by circular dichroism.
• Platinated dimer properties differ from those of RNase A N- and C-swapped dimers.
• Platinated monomer, dimer and trimer keep a significant ribonuclease activity.

The reaction between cis-diamminedichloroplatinum(II) (CDDP), cisplatin, a common anticancer drug, and bovine pancreatic ribonuclease (RNase A), induces extensive protein aggregation, leading to the formation of one dimer, one trimer and higher oligomers whose yields depend on cisplatin/protein ratio. Structural and functional properties of the purified platinated species, together with their spontaneous dissociation and thermally induced denaturation, have been characterized. Platinated species preserve a significant, although reduced, ribonuclease activity. The high resistance of the dimers against dissociation and the different thermal unfolding profiles suggest a quaternary structure different from those of the well-known swapped dimers of RNase A.

RNase A incubation in the presence of an excess of cisplatin induces the formation of platinated oligomers with structural and functional properties distinct from those of the previously characterized oligomers of the same protein.Figure optionsDownload as PowerPoint slide