title: Site-Specific Conjugation of Peptides and Proteins via Rebridging of Disulfide Bonds Using the Thiol-Yne Coupling Reaction.
abstract: Herein, we describe an extension of our previously reported photomediated disulfide rebridging methodology to the conjugation of peptides and proteins. The methodology proved to be reproducible with various alkynes and different peptides. This study includes the first rebridging of the disulfide bond of a peptide through a thiol-yne reaction with a cyclooctyne. In all cases, the rebridging was proven by MS analyses and confirmed by the absence of olefinic protons on (1)H NMR spectra of the resulting products. Finally, this one-pot reduction thiol-yne conjugation was successfully applied to an antibody Fab fragment with a promising conversion, which set a good ground for the future syntheses of new protein and antibody conjugates.
authors.forename: Nils
authors.initials: N
authors.lastname: Griebenow
authors.affiliation: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Dilmaç
authors.forename: Simone
authors.initials: S
authors.lastname: Greven
authors.affiliation: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany.|Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT) , Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
mesh_terms: D004220:Disulfides / Q000737:chemistry*; D013058:Mass Spectrometry; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D004220:Disulfides; D010455:Peptides; D011506:Proteins; D013438:Sulfhydryl Compounds