Mapping the protein-binding sites for iridium(iii)-based CO-releasing molecules

Area of Science:

• Inorganic Chemistry
• Biochemistry
• Chemical Biology

Background:

• Carbon monoxide-releasing molecules (CO-RMs) are investigated for therapeutic potential.
• Understanding the interaction of CO-RMs with biological targets is crucial for drug development.

Purpose of the Study:

• To elucidate the reaction mechanism between an iridium-based CO-RM, Cs2IrCl5CO, and a model protein, bovine pancreatic ribonuclease.
• To identify specific binding sites and the fate of the CO ligand upon reaction.

Main Methods:

• A multidisciplinary approach combining mass spectrometry, Raman microspectroscopy, circular dichroism, and X-ray crystallography.
• Detailed structural and chemical analysis of the reaction products.

Main Results:

• Iridium-compound fragments were found to bind to the N-terminal amine and near histidine and methionine side chains of the protein.
• The carbon monoxide ligand was observed to be retained for an extended period.
• The study identified specific protein targets for iridium-based CO-RMs.

Conclusions:

• The findings provide valuable insights into the mechanism of action of iridium-based CO-RMs.
• This research aids in the rational design of CO-RMs for specific biological applications and therapeutic strategies.