Development of Stable Phosphohistidine Analogues

Laboratory of Synthetic Protein Chemistry, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Journal of the American Chemical Society (Impact Factor: 11.44). 09/2010; 132(41):14327-9. DOI: 10.1021/ja104393t
Source: PubMed

ABSTRACT Protein phosphorylation is one of the most common and extensively studied posttranslational modifications (PTMs). Compared to the O-phosphorylation of Ser, Thr, and Tyr residues, our understanding of histidine phosphorylation is relatively limited, particularly in higher eukaryotes, due to technical difficulties stemming from the intrinsic instability and isomerism of phosphohistidine (pHis). We report the design and synthesis of stable and nonisomerizable pHis analogues. These pHis analogues were successfully utilized in solid-phase peptide synthesis and semi-synthesis of histone H4. Significantly, the first antibody that specifically recognizes pHis was obtained using the synthetic peptide as the immunogen.

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