Laboratory of Synthetic Protein Chemistry, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
J Am Chem Soc. 2010 Oct 20;132(41):14327-9. doi: 10.1021/ja104393t.
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.
蛋白质磷酸化是最常见和广泛研究的翻译后修饰（PTMs）之一。与丝氨酸、苏氨酸和酪氨酸残基的 O-磷酸化相比，由于磷酸组氨酸（pHis）固有不稳定性和异构性带来的技术困难，我们对组氨酸磷酸化的理解相对有限，特别是在高等真核生物中。我们报告了稳定且不可异构化的 pHis 类似物的设计和合成。这些 pHis 类似物成功地用于固相肽合成和组蛋白 H4 的半合成。值得注意的是，使用合成肽作为免疫原获得了特异性识别 pHis 的第一抗体。
