US scientists can now compare molecular warheads that inactivate proteins.

Chromophore assisted light inactivation (CALI) of proteins involves generating highly reactive species (often singlet oxygen) from a chromophore (the warhead) using light. The reactive species damages the target protein, inactivating its biological function. Thomas Kodadek, a chemical biologist at University of Texas Southwestern Medical Centre, explained that CALI can be used to 'knock-out the function of a protein to validate pharmaceutical targets or alternatively provide temporal control of protein inactivation for mechanistic studies.'

In CALI, chromophores (red) produce reactive species to inactivate a target protein

Organic chromophores often react with the reactive species they produce, limiting their effectiveness as CALI warheads. In this new research, Kodadek and his co-workers have developed a system for comparing warhead effectiveness. The system allows different chromophores to be covalently attached to a standard target protein through a simple coupling mechanism. This allows the chromophore efficiencies to be compared by measuring the remaining activity of the target. 

Comparative experiments showed a ruthenium-based chromophore to be a more effective warhead than the commonly used organic dye fluorescein. The scientists demonstrated that the ruthenium chromophore can enter cells and inactivate a target, opening up the possibility of CALI experiments on living cells as well as cell extracts.

Russell Johnson