A photocaged protease inhibitor was designed using a synthesized peptidomimetic molecule with a nitrile group used for attachment to the 'cage', a ruthinium-based complex in this case. The aim is to develop this technology as a cancer drug that can be activated in proximity to the cancerous tissue with light. The protease inhibitor is meant to target a cysteine cathepsin, which is overexpressed in many cancers. Additionally, the ruthinium molecule also has potential bioactivity since it can covalently bind DNA. This complex showed excellent stability in the dark and rapid release of the inhibitor upon irradiation with light.
Some caspase inhibitors bind to cysteines in the dimer interface of the enzyme. Others might bind to the catalytic cysteine. I wonder if it would be beneficial to photocage caspase inhibitors (and/or activators once they are developed).
ReplyDelete