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Post-translational site-selective protein backbone α-deuteration, Dr V.Chudasama and Prof. B.Davis

18 September 2018

Graphical_abstract

Isotopic replacement applications in proteins are largely limited to biosynthetic strategies or at exchangeable (e.g. N–H/D) labile sites only. Thus the development of post-biosynthetic C–1H→C–2H/D replacement in proteins could enable the use of labelling in a multitude of fields/areas where the aforementioned strategies are either not useful or not even possible.

In this manuscript published in Nature Chemical Biology (https://rdcu.be/6Whs), Dr Vijay Chudasama (UCL, Department of Chemistry) and Prof. Ben Davis FRS (Oxford University, Department of Chemistry) describe a chemical method for selective protein α‑carbon-deuteration (proceeding from Cys to dehydroalanine (Dha) to deutero-Cys) allowing overall 1H→2H/D exchange at a non-exchangeable backbone site. The ready application of this developed technology on existing, intact protein constructs (without specialized culture or genetic methods) suggests this C–D labelling strategy to be an impressive tool in future protein mechanism, structure, biotechnology and medicine studies.

“It has been great to collaborate on this project with Ben; it’s been a long road to make our vision a reality but we did get there! We are very thankful to all the co-workers that have contributed to this work and very pleased with the end result in that the technology is highly robust and will hopefully be used to enable fundamental discoveries in Chemical Biology, Medicine and Biotechnology.” – Dr Vijay Chudasama

“It’s been a fun, joint journey through this intriguing mechanistic problem, which was first highlighted by some beautiful prior observations of Vijay’s on unusual protein intermediates. The range of chemistries that are starting to be precisely applied to proteins will mean, I think, that such mechanistic work on protein chemistry methodology will become increasingly common and it was nice to highlight how this might be achieved.” – Prof. Ben Davis FRS