31OCT2024 New work published by the Jarvis Group presents a dual purpose non-canonical amino acid that provides both a metal binding site and a bioorthogonal reactive site, opening up new functionality for protein engineering. DNA, our genetic code, is a blueprint encoding the amino acids needed to make all the enzymes and proteins required for life. In humans there are just 20 amino acids used - the so-called canonical amino acids (cAAs). Since the early 2000s, however, researchers working in the new field of Genetic Code Expansion have been able to add more than 250 non-canonical amino acids (ncAAs) that vastly increase the chemical diversity of proteins. The resulting ability to produce new designer proteins with target chemical groups, and therefore function, brings with it huge possibilities for innovation in life sciences, medicine and industry. For example, new antibody drug conjugates containing ncAAs are currently undergoing clinical trials as cancer therapies, and new photoenzymes containing ncAAs have been designed. The new dual purpose non-canonical amino acid. Now, a new paper from the School of Chemistry’s Jarvis group presents, for the first time, the incorporation of a non-canonical amino acid into a protein that contains both a bipyridine, to act as a metal binding site, and a triazine, which acts as a bioorthogonal handle for further protein modification. The team were able to make luminescent probes which light up on irradiation using iridium bound to the bipyridine. The colour of the light emitted changes when the bioorthogonal handle reacts with its payload (for example, a drug), whilst the iridium may help to speed up that reaction. Using genetic code expansion allows this dual-purpose amino acid to be encoded into any protein, offering a novel tool for bioscience applications.Looking to the future, the team believe this ncAA could be used in applications as diverse as catalysis with varied metals and therapeutic applications including photodynamic therapy, theranostics or dual-modality imaging. The work was conducted in collaboration with a team led by Dr Valery Kozhevnikov from Northumbria University. It’s great to see what started off as a small idea shared at a conference in Edinburgh back in 2019 grow, through the work of Andrey, Richard and Graham, into a new tool for biosciences that we are able to share with the community.Flexible funding provided through the UKRI FLF scheme was invaluable in allowing this project to continue and reach a fruitful end point. Dr Amanda Jarvis Senior Lecturer and UKRI Future Leaders Fellow The Jarvis group combine transition metal catalysts with biological architecture to create new metalloproteins with unique properties for applications in catalysis, biotechnology and health. The group’s expertise spans from genetic code expansion and bioconjugation technology to bioinorganic chemistry and catalysis. Instrumental to their work are the analytical facilities provided through the School of Chemistry, including Mass Spectrometry, ACIS and NMR.The paper is published in Angewandte Chemie International Edition - read it at the link below. Read “A Dual-Purpose Non-Canonical Amino Acid for the Expanded Genetic Code: Co… Read more about the Jarvis Group. Publication date 31 Oct, 2024
