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Neighbor-directed histidine N (?)-alkylation: A route to imidazolium-containing phosphopeptide macrocycles.

ABSTRACT: Our recently discovered, selective, on-resin route to N(?)-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(?)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.

SUBMITTER: Qian WJ

PROVIDER: S-EPMC4865893 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Neighbor-directed histidine N (τ)-alkylation: A route to imidazolium-containing phosphopeptide macrocycles.

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

Biopolymers 20151101 6

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 ...[more]

PMID: 26152807

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