title: Histidine-Directed Arylation/Alkenylation of Backbone N-H Bonds Mediated by Copper(II).
abstract: Chemical modification of proteins and peptides represents a challenge of reaction design as well as an important biological tool. In contrast to side-chain modification, synthetic methods to alter backbone structure are extremely limited. In this communication, copper-mediated backbone N-alkenylation or N-arylation of peptides and proteins by direct modification of natural sequences is described. Histidine residues direct oxidative coupling of boronic acids at the backbone NH of a neighboring amino acid. The mild reaction conditions in common physiological buffers, at ambient temperature, are compatible with proteins and biological systems. This simple reaction demonstrates the potential for directed reactions in complex systems to allow modification of N-H bonds that directly affect polypeptide structure, stability, and function.
authors.affiliation: Department of Chemistry, Rice University , Houston, Texas 77005, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohata
authors.affiliation: Department of Chemistry, Rice University , Houston, Texas 77005, United States.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Minus
authors.affiliation: Department of Chemistry, Rice University , Houston, Texas 77005, United States.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Abernathy
authors.affiliation: Department of Chemistry, Rice University , Houston, Texas 77005, United States.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Ball
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry*; D010084:Oxidation-Reduction; D013973:Thyrotropin-Releasing Hormone / Q000737:chemistry*
chemical_list: D000475:Alkenes; D001897:Boronic Acids; D006841:Hydrocarbons, Aromatic; D006639:Histidine; D013973:Thyrotropin-Releasing Hormone; D003300:Copper; D009584:Nitrogen