title: Chemoproteomic Evaluation of the Polyacetylene Callyspongynic Acid.
abstract: Polyacetylenes are a class of alkyne-containing natural products. Although potent bioactivities and thus possible applications as chemical probes have already been reported for some polyacetylenes, insights into the biological activities or molecular mode of action are still rather limited in most cases. To overcome this limitation, we describe the application of the polyacetylene callyspongynic acid in the development of an experimental roadmap for characterizing potential protein targets of alkyne-containing natural products. To this end, we undertook the first chemical synthesis of callyspongynic acid. We then used in situ chemical proteomics methods to demonstrate extensive callyspongynic acid-mediated chemical tagging of endoplasmic reticulum-associated lipid-metabolizing and modifying enzymes. We anticipate that an elucidation of protein targets of natural products may serve as an effective guide to the development of subsequent biological assays that aim to identify chemical phenotypes and bioactivities.
authors.affiliation: Chemische Biologie, ZMB, Universität Duisburg-Essen, Universitätsstr. 2, 45117 Essen (Germany).
authors.forename: Sabrina
authors.initials: S
authors.lastname: Nickel
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ (UK).
authors.forename: Remigiusz A
authors.initials: RA
authors.lastname: Serwa
authors.affiliation: Chemische Biologie, ZMB, Universität Duisburg-Essen, Universitätsstr. 2, 45117 Essen (Germany).
authors.forename: Farnusch
authors.initials: F
authors.lastname: Kaschani
authors.affiliation: Chemische Biologie, ZMB, Universität Duisburg-Essen, Universitätsstr. 2, 45117 Essen (Germany).
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ninck
authors.affiliation: Chemische Biologie, ZMB, Universität Duisburg-Essen, Universitätsstr. 2, 45117 Essen (Germany).
authors.forename: Susanne
authors.initials: S
authors.lastname: Zweerink
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ (UK).
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
authors.affiliation: Chemische Biologie, ZMB, Universität Duisburg-Essen, Universitätsstr. 2, 45117 Essen (Germany). markus.kaiser@uni-due.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Kaiser
mesh_terms: D000480:Alkynes / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D053279:Polyynes / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D000480:Alkynes; D001688:Biological Products; D011506:Proteins; C464988:callyspongynic acid; D053279:Polyynes
keywords: alkynes; click chemistry; drug discovery; natural products; proteomics