title: Preparation of Fluorescent Microcystin Derivatives by Direct Arginine Labelling and Their Biological Evaluation.
abstract: Microcystin is the most prevalent toxin produced by cyanobacteria and poses a severe threat to livestock, humans and entire ecosystems. We report the preparation of a series of fluorescent microcystin derivatives by direct arginine labelling of the unprotected peptides at the guanidinium side chain. This new method allows a simple late-stage diversification strategy for native peptides devoid of protecting groups under mild conditions. A series of fluorophores were conjugated to microcystin-LR in good to very good yield. The fluorescent probes displayed biological activity comparable to that of unlabelled microcystin, in both phosphatase inhibition assays and toxicity tests on the crustacean Thamnocephalus platyurus. In addition, we demonstrate that the fluorescent probes penetrated Huh7 cells. Whole-animal imaging was performed on T. platyurus: labelled compound was mainly observed in the digestive tract.
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel (Switzerland).
authors.forename: Verena
authors.initials: V
authors.lastname: Grundler
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Gründenstrasse 40, 4132 Muttenz (Switzerland).
authors.forename: Susanne
authors.initials: S
authors.lastname: Faltermann
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Gründenstrasse 40, 4132 Muttenz (Switzerland).|Department of Environmental Systems Science, Swiss Federal Institute of Technology (ETHZ), Institute of Biogeochemistry and Pollution Dynamics, Universitätsstrasse 16, 8092 Zürich (Switzerland).
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel (Switzerland). karl.gademann@unibas.ch.
authors.forename: Karl
authors.initials: K
authors.lastname: Gademann
mesh_terms: D000818:Animals; D033202:Anostraca / Q000378:metabolism; D001120:Arginine / Q000737:chemistry*; D001692:Biological Transport; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D052998:Microcystins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D052998:Microcystins; C078588:microcystin; D001120:Arginine; D010749:Phosphoprotein Phosphatases
keywords: chemical biology; cyanobacteria; fluorescent probes; microbiology; toxicology