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

Journal Article · Tue Jul 07 00:00:00 EDT 2015 · Biopolymers

DOI:https://doi.org/10.1002/bip.22698· OSTI ID:1228107

Qian, Wen-Jian ^[1]; Park, Jung-Eun ^[2]; Grant, Robert ^[3]; Lai, Christopher C. ^[1]; Kelley, James A. ^[1]; Yaffe, Michael B. ^[3]; Lee, Kyung S. ^[2]; Burke, Terrence R. ^[1]

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1. National Cancer Inst., Frederick, MD (United States)
2. National Cancer Inst., Bethesda, MD (United States)
3. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

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. These cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Furthermore, neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 1228107
• Journal Information: Biopolymers, Vol. 104, Issue 6; ISSN 1097-0282
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

PLk1
polo kinase
polo-box domain
crystal structure
cationic dialkyl histidine
peptide macrocycles
phosphopeptides