title: Chemo- and Regioselective Ethynylation of Tryptophan-Containing Peptides and Proteins.
abstract: Ethynylation of various tryptophan-containing peptides and a single model protein was achieved using Waser's reagent, 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1 H)-one (TIPS-EBX), under gold(I) catalysis. It was demonstrated by NMR that the ethynylation occurred selectively at the C2-position of the indole ring of tryptophan. Further, MS/MS showed that the tryptophan residues could be modified selectively with ethynyl functionalities even when the tryptophan was present as a part of the protein. Finally, the terminal alkyne was used to label a model peptide with a fluorophore by means of copper-catalyzed click chemistry.
authors.affiliation: Novo Nordisk A/S, Novo Nordisk Park, 2760, Måløv, Denmark. mbyh@novonordisk.com.
authors.forename: Morten Borre
authors.identifier: http://orcid.org/0000-0003-2538-6854
authors.initials: MB
authors.lastname: Hansen
authors.affiliation: Novo Nordisk A/S, Novo Nordisk Park, 2760, Måløv, Denmark.
authors.forename: František
authors.initials: F
authors.lastname: Hubálek
authors.affiliation: Carbon Dioxide Activation Center (CADIAC), Interdisplinary Nanoscience Center and Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup
authors.affiliation: Novo Nordisk A/S, Novo Nordisk Park, 2760, Måløv, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoeg-Jensen
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D057930:Click Chemistry; D006046:Gold / Q000737:chemistry; D006847:Hydrocarbons, Iodinated / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D017646:Organosilicon Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry*
chemical_list: C000608689:1-((triisopropylsilyl)ethynyl)-1,2-benziodoxol-3(1 H)-one; D000480:Alkynes; D006847:Hydrocarbons, Iodinated; D007202:Indicators and Reagents; D017646:Organosilicon Compounds; D010455:Peptides; D011506:Proteins; D006046:Gold; D014364:Tryptophan
keywords: C−H activation; alkynylation; chemoselectivity; gold; peptides