New tool opens the door to light driven in-cell chemistry

A team of scientists, led by Professor Ben Davis, Science Director for Next Generation Chemistry at The Franklin, and Professor Veronique Gouverneur at Oxford University have created a light-activated system that allows new side-chains to be grafted on to proteins, paving the way for a host of applications in areas such as drug development or vaccines. The study is published in the journal Nature.

This work represents a large collaborative effort from a number of Oxford-based research groups, including Professors Ben Davis, Shabaz Mohammed, Andrew Baldwin, Akane Kawamura, Richard Compton, and Veronique Gouverneur. The research builds on previous work that proved the concept of side-chain grafting in protein modification. The new work makes this process substantially more efficient, introduces the idea of using light to control the process, and allows the use of latently reactive side-chains.

Professor Ben Davis, of the Rosalind Franklin Institute and Oxford University’s Department of Chemistry, is a co-senior author of this paper and this year’s recipient of the Davy medal awarded by the Royal Society. He said, ‘There’s a lot of work taking place on gene editing – trying to reprogram biology from the “recipe” onwards. But while genes are often associated with function nowadays, proteins – and the things they make – are the molecules that really make things happen in biology. This work looks at methods for editing proteins, all of which boils down to making and breaking bonds in molecules. Nature does this beautifully, but only with limited scope, using enzymes as catalysts – we set out here to create a method using chemical catalysts.’

Read the full science highlight on the work here.

Read the publication: Josephson et al. Mild, Light-Driven, Posttranslational Installation of Reactive Protein Side-Chains Nature (2020)