Our recently discovered, selective, on-resin route to N(s)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Neighbor-directed histidine N(s)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.
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See: Neighbor-Directed Histidine N (s)–Alkylation: A Route to Imidazolium-Containing Phosphopeptide Macrocycles-Biopolymers by Wen-Jian Qian, Jung-Eun Park, Robert Grant, Christopher C. Lai, James A. Kelley, Michael B. Yaffe, Kyung S. Lee and Terrence R. Burke Jr. in Peptide Science, 2015, 104, 663–673.3.