University of dundee kiss of death
A kiss of death to drug the ‘undruggable’
Scientists at the University of Dundee have reported a major breakthrough in targeting the causes of many diseases, using a ‘kiss of death’ to destroy proteins which had previously been regarded as ‘undruggable’.
Much is known about proteins such as Ras and Myc, which are known to be culpable in human cancer, and Huntingtin, which causes Huntingdon’s disease, but as yet they have proved stubbornly resistant to efforts to find ways of tackling them with drugs.
Now researchers led by Professor Alessio Ciulli in the School of Life Sciences at Dundee have found a way of targeting similar proteins, using a small-molecule approach in an unconventional way to target ‘bad’ proteins by binding them to neutralising agents to start a process of degradation, and thereby removing them entirely.
“We know of many proteins which are active in causing diseases, but which we have been unable to block from going ‘rogue’ or to stop them when they do,” said Professor Ciulli.
“The major problem is that we have been unable to find the small molecules which can successfully bind to these proteins and at the same time hamper their function. It is a highly complex area – these proteins can often fool regulators within the cell and be extremely difficult to pin down with inhibitors.
“Research in our lab in the past few years has contributed towards establishing a different approach, one that has been theorised for many years but which is only now fully realised by this latest work. Instead of using the small molecule to try and disable the bad protein, we have developed a way of modifying it so that it can be used to attract the neutralising proteins, which then bind to their bad neighbour and act against it, starting a cascade process of degradation.