title: Irreversible Cysteine-Selective Protein Labeling Employing Modular Electrophilic Tetrafluoroethylation Reagents.
abstract: Fluoroalkylation reagents based on hypervalent iodine are widely used to transfer fluoroalkyl moieties to various nucleophiles. However, the transferred groups have so far been limited to simple structural motifs. We herein report a reagent featuring a secondary amine that can be converted to amide, sulfonamide, and tertiary amine derivatives in one step. The resulting reagents bear manifold functional groups, many of which would not be compatible with the original synthetic pathway. Exploiting this structural versatility and the known high reactivity toward thiols, the new-generation reagents were used in bioconjugation with an artificial retro-aldolase, containing an exposed cysteine and a reactive catalytic lysine. Whereas commercial reagents based on maleimide and iodoacetamide labeled both sites, the iodanes exclusively modified the cysteine residue. The study thus demonstrates that modular fluoroalkylation reagents can be used as tools for cysteine-selective bioconjugation.
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.|Institute of Organic Chemistry and Biochemistry, v.v.i., Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Václavík
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Zschoche
authors.affiliation: Institute of Organic Chemistry and Biochemistry, v.v.i., Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Klimánková
authors.affiliation: CF Plus Chemicals s.r.o., Kamenice 771/34, 625 00, Brno, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Matoušek
authors.affiliation: Institute of Organic Chemistry and Biochemistry, v.v.i., Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Petr
authors.identifier: http://orcid.org/0000-0002-0888-7465
authors.initials: P
authors.lastname: Beier
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Togni
mesh_terms: D000588:Amines / Q000737:chemistry; D002234:Carbodiimides / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D007455:Iodine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: C518491:1-ethyl-3-(3-(diethylamino)propyl)carbodiimide; D000588:Amines; D002234:Carbodiimides; D011506:Proteins; D013438:Sulfhydryl Compounds; D007455:Iodine; D008239:Lysine; D003545:Cysteine
keywords: bioconjugation; cysteine; enzymes; fluorine; fluoroalkylation; hypervalent iodine