Periodic Reporting for period 1 - PyroPhosphoProtein (Site-selective chemical pyrophosphorylation of proteins using tag-and-modify approach.)
Reporting period: 2016-04-01 to 2018-03-31
Until now, many proteins have been found to be pyrophosphorylated in vitro but the real significance of protein pyrophosphorylation in vivo remains poorly understood due to lack of chemical biology tools to study this novel post-translational modification. Here we developed a novel method for preparation of pure, well defined pyrophosphorylated proteins and their stable analogs offering long awaited tool for probing of pyrophosphorylation function.
Previously, β,γ-C,S (thia-Michael addition); β,γ-C,Se (selena-Michael addition) and β,γ-C,C (radical addition) bonds were formed post-translationally through Dha modification in proteins. Here, β,γ-C,N (aza-Michael addition) was described providing a novel protein conjugation method as well as a general tool for installing histidine mimics into proteins. These mimics were shown to be useful in dissecting histidine contribution to enzyme activity.
The project complied with the basic principles of the European Research Area by fostering research training, collaboration, mobility and knowledge transfer. It has enabled scientific and personal development of individuals and further promoted Europe as centre of research excellence.