Oxaliplatin vs. cisplatin: competition experiments on their binding to lysozyme

Area of Science:

• Biochemistry
• Structural Biology
• Drug Discovery

Background:

• Platinum-based drugs like oxaliplatin and cisplatin are crucial in cancer chemotherapy.
• Understanding their interaction with biological molecules, such as proteins, is vital for drug development.

Purpose of the Study:

• To investigate the binding interactions of oxaliplatin and cisplatin with hen egg white lysozyme.
• To determine the binding sites and affinities of these platinum drugs on a model protein.

Main Methods:

• Electrospray ionization mass spectrometry (ESI MS) for adduct identification.
• Surface plasmon resonance (SPR) for assessing binding affinities.
• Thermal shift assays to analyze protein stability changes upon drug binding.
• X-ray crystallography to determine the three-dimensional structure of the platinum-protein adducts.

Main Results:

• Formation of bis-platinum adducts with hen egg white lysozyme by both oxaliplatin and cisplatin, albeit in low quantities.
• X-ray structures revealed distinct, non-overlapping surface binding sites for the two platinum drugs.
• Similar binding affinities were observed for both drugs under the experimental conditions.

Conclusions:

• Oxaliplatin and cisplatin exhibit different reactivity profiles towards hen egg white lysozyme.
• The platinum drugs do not compete for the same binding sites on the model protein.
• Structural insights into drug-protein interactions can inform the design of more effective platinum-based chemotherapeutics.