title: Targeted Diazotransfer Reagents Enable Selective Modification of Proteins with Azides.
abstract: In chemical biology, azides are used to chemically manipulate target structures in a bioorthogonal manner for a plethora of applications ranging from target identification to the synthesis of homogeneously modified protein conjugates. While a variety of methods have been established to introduce the azido group into recombinant proteins, a method that directly converts specific amino groups in endogenous proteins is lacking. Here, we report the first biotin-tethered diazotransfer reagent DtBio and demonstrate that it selectively modifies the model proteins streptavidin and avidin and the membrane protein BioY on cell surface. The reagent converts amines in the proximity of the binding pocket to azides and leaves the remaining amino groups in streptavidin untouched. Reagents of this novel class will find use in target identification as well as the selective functionalization and bioorthogonal protection of proteins.
authors.affiliation: Chemical Biology II, Stratingh Institute for Chemistry, University of Groningen , Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Jonas
authors.initials: J
authors.lastname: Lohse
authors.affiliation: Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute , Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Lotteke J Y M
authors.initials: LJYM
authors.lastname: Swier
authors.affiliation: Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute , Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Oudshoorn
authors.affiliation: Chair for Proteomics and Bioanalytics, WZW, Technical University of Munich , Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany.
authors.forename: Guillaume
authors.identifier: 0000-0002-4782-4029
authors.initials: G
authors.lastname: Médard
authors.affiliation: Chair for Proteomics and Bioanalytics, WZW, Technical University of Munich , Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany.|Center for Integrated Protein Science Munich (CIPSM) , Butenandtstraße 5, 81377 Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
authors.affiliation: Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute , Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Slotboom
authors.affiliation: Chemical Biology II, Stratingh Institute for Chemistry, University of Groningen , Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Martin D
authors.identifier: 0000-0003-4660-2974
authors.initials: MD
authors.lastname: Witte
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001360:Avidin / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry; D004926:Escherichia coli / Q000737:chemistry*; D013294:Lactococcus lactis / Q000737:chemistry*; D008958:Models, Molecular; D019809:Streptavidin / Q000737:chemistry*
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000480:Alkynes; D001386:Azides; D001426:Bacterial Proteins; D001896:Boron Compounds; D001360:Avidin; D001710:Biotin; D019809:Streptavidin