Stable analogues of phosphohistidine
The post-translational modification of proteins is an ubiquitous mechanism of regulation and signalling in living organisms. Protein O-phosphorylation on serine, threonine and tyrosine residues is well established as a dominant mechanism of protein modification for signalling in mammalian cells. In contrast, in many bacteria, the process of two-component regulation employs phosphorylation of histidine and aspartate residues to the same effect. In both cases, structural and enzymatic studies involving the
We have generated a triazole analogue of phosphohistidine which is fully compatible with the Fmoc-strategy for solid-phase peptide synthesis and are now applying this analogue in a variety of enzymatic studies as well as investigating the potential role of canonical phosphotyrosine-binding domains in recognition of phosphohistidine.
Triazines, a slow entrant in the bioorthogonal reaction race
We have recently described the synthesis and reaction of triazine-containing amino acids. These react with many of the same bio-orthogonal reaction partners as azides and the more reactive tetrazines including biocyclononynes but do so orders of magnitude more slowly. This inspired our choice of cover art which was created by a Leeds undergraduate student, Zach Owen, which shows the pseudo-proverbial race of 'the sloth and the hare'.
Recent publications in this area
Strain-promoted reaction of 1,2,4-triazines with bicyclononynes
Katherine A. Horner, Nathalie M. Valette & Michael E. Webb Chem.—Eur. J. (2015) 21 14376-81
Evaluation of the interaction between phosphohistidine analogues and phosphotyrosine-binding domains
Tom E McAllister, Katherine A. Horner & Michael E Webb ChemBioChem (2014) 15 1088-1091
Triazole phosphohistidine analogues compatible with the Fmoc-strategy
Tom E. McAllister and Michael E Webb. Org. Biomol. Chem. (2012) 10 4043-4049
Fmoc-chemistry of stable analogues of phosphohistidine.
Tom E McAllister, Michael G Nix and Michael E Webb Chem. Commun. (2011) 47, 1297-1299