title: Glycine fluoromethylketones as SENP-specific activity based probes.
abstract: We report here the synthesis and biochemical properties of a new peptidyl activity-based probe 1 for SUMO proteases, SENPs. The activity-based probe has at its C terminus a glycine-derived fluoromethylketone moiety as a reactive group designed to target the active-site cysteine of SENPs. Based on a study of the interactions between SENPs and SUMOs, we introduced further design elements that allow the activity-based probe to selectively target SENPs at low micromolar to high nanomolar concentrations. Moreover, 1 out-competes SUMO1 from the reversible SUMO1-SENP1 complex, thus suggesting that 1 and SUMO1 share a common binding site on SENP1.
authors.affiliation: Department of Chemistry, Technical University of Munich, Garching, Germany.
authors.forename: Cristian
authors.initials: C
authors.lastname: Dobrotă
authors.forename: Domenico
authors.initials: D
authors.lastname: Fasci
authors.forename: Niculina D
authors.initials: ND
authors.lastname: Hădade
authors.forename: Gheorghe-Doru
authors.initials: GD
authors.lastname: Roiban
authors.forename: Cristina
authors.initials: C
authors.lastname: Pop
authors.forename: Veronika M
authors.initials: VM
authors.lastname: Meier
authors.forename: Ioana
authors.initials: I
authors.lastname: Dumitru
authors.forename: Mihaela
authors.initials: M
authors.lastname: Matache
authors.forename: Guy S
authors.initials: GS
authors.lastname: Salvesen
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Funeriu
mesh_terms: D001665:Binding Sites; D010450:Endopeptidases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D007659:Ketones; D011994:Recombinant Proteins; D010450:Endopeptidases; D005998:Glycine