title: Copper-free Sonogashira cross-coupling for functionalization of alkyne-encoded proteins in aqueous medium and in bacterial cells.
abstract: Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddition reaction ("click chemistry"), have provided chemical tools to study biomolecular dynamics and function in living systems. Despite its prominence in organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for biological applications has not been reported. In this work, we report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide range of aromatic groups including fluorophores and fluorinated aromatic compounds can be readily introduced into the HPG-containing ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chemistry.
authors: Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260-3000, United States.
authors: Nan
authors: N
authors: Li
authors: Reyna K V
authors: RK
authors: Lim
authors: Selvakumar
authors: S
authors: Edwardraja
authors: Qing
authors: Q
authors: Lin
mesh_terms: D000480:Alkynes / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli / Q000166:cytology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry; D011487:Protein Conformation; D012995:Solubility; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000737:chemistry*
chemical_list: D000480:Alkynes; D001426:Bacterial Proteins; D025801:Ubiquitin; C551041:homopropargylglycine; D014867:Water; D010165:Palladium; D005998:Glycine