Development of Non-Hydrolyzable Inositol Pyrophosphate Analogs and Their Application in the Identification of Inositol Pyrophosphate Binding Partners.
Biochemistry
Organic Molecular Chemistry - Synthesis and Characterisation
Final Report Abstract
Overall, the postdoctoral research at Princeton University lead to new discoveries in the field of inositol polyphosphate signaling. In particular, novel non-hydrolysable analogs of these compounds were prepared enabling the conformational characterization of these highly interesting second messengers in solution. These results lead finally to the theory of the ‘switch of selectivity’ of these species towards their enzymes depending on the local pH and metal ion concentrations – an assumption that needs further investigations. In addition, a biochemical characterization of these molecules was performed concluding their superb mimicking properties in comparison to the parent inositol pyrophosphate compounds. The picture was then completed by the crystallization of the bisphosphonate analogs with IP7K – a kinase involved in pyrophosphate biosynthesis. Currently, further investigations on this topic are ongoing at the Fiedler laboratory.
Publications
- "Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues." Chem. Eur. J. 2016, 22, 12406-12414
Anastasia Hager, Mingxuan Wu, Huanchen Wang, Nathaniel W. Brown Jr., Stephen B Shears, Nicolás Veiga, Dorothea Fiedler
(See online at https://doi.org/10.1002/chem.201601754)
