If you're a researcher planning to cure a disease by removing a specific protein, you'll need the therapy to be selective. Hit the wrong target and you'll make things worse - not better. With this in mind, Japanese scientists have identified a light-activated agent that seeks out and destroys a particular protein.

When irradiated with visible light Toshima's porphyrin derivative selectively degrades a hormone receptor protein

Kazunobu Toshima and co-workers at Keio University, Tokyo, Japan, have discovered a porphyrin derivative that selectively fragments a hormone receptor protein upon irradiation with visible light. 

Whilst porphyrin derivatives have been used in photodynamic therapy (PDT) to target cancer cell DNA, Toshima's research is the first time the approach has been applied to proteins. 'We've proved that certain porphyrins degrade not only DNA but also proteins with high selectivity. This could lead to new drugs for PDT,' says Toshima.

Toshima's porphyrin works under mild conditions. What's more, only catalytic amounts of the porphyrin are needed to effectively degrade the target protein, since the protein is actually damaged by reactive oxygen species produced by the porphyrin when it is irradiated with light. 

The porphyrin is structurally similar to the hormone oestradiol - one of the oestrogens. Toshima suggests this structural similarity could be the basis of the high selectivity for the target protein, human oestrogen receptor-alpha. The porphyrin should have a higher affinity, and therefore spatial proximity, to oestrogen receptor proteins, he says. 'The life-time of reactive oxygen species is very short so the selectivity is generated by the location of the porphyrin agent.'

'This is the first example of target-selective protein degradation by visible wavelength photo-irradiation using a porphyrin derivative,' comments Aiping Zhu, an expert in biomolecule photochemistry at the University of Michigan, Ann Arbor, US. 'These exciting results open up a route for organic photochemical agents as protein photocleavers to control specific functions of certain proteins.' 

Russell Johnson