Neighbor-directed histidine N (τ)-alkylation: A route to imidazolium-containing phosphopeptide macrocycles.
Our recently discovered, selective, on-resin route to N(τ)-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(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.
['Qian|Wen-Jian|WJ|', 'Park|Jung-Eun|JE|', 'Grant|Robert|R|', 'Lai|Christopher C|CC|', 'Kelley|James A|JA|', 'Yaffe|Michael B|MB|', 'Lee|Kyung S|KS|', 'Burke|Terrence R|TR|']
D000478:Alkylation D018360:Crystallography, X-Ray D006639:Histidine D007093:Imidazoles D047028:Macrocyclic Compounds D010748:Phosphopeptides
Plk1 cationic dialkyl histidine crystal structure peptide macrocycles, phosphopeptides polo kinase polo-box domain