title: Investigating the Toxicity of the Aeruginosin Chlorosulfopeptides by Chemical Synthesis.
abstract: Harmful algal blooms are becoming more prevalent all over the world, and identification and mechanism-of-action studies of the responsible toxins serve to protect ecosystems, livestock, and humans alike. In this study, the chlorosulfopeptide aeruginosin 828A, which rivals the well-known toxin microcystin LR in terms of crustacean toxicity, has been synthesized for the first time. Furthermore, three congeners with different permutations of the chloride and sulfate groups were prepared, thereby enabling toxicity studies without the risk of contamination by other natural toxins. Toxicity assays with the sensitive crustacean Thamnocephalus platyurus demonstrated that the introduction of a sulfate group leads to pronounced toxicity, and NMR spectroscopic evidence suggests that the chloride substituent modulates the conformation, which in turn might influence protease inhibition.
authors.affiliation: Department Chemie, Universität Basel, St. Johanns-Ring 19, 4056, Basel, Switzerland.|Department Chemie, Universität Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Scherer
authors.affiliation: Department Chemie, Universität Basel, St. Johanns-Ring 19, 4056, Basel, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Bezold
authors.affiliation: Department Chemie, Universität Basel, St. Johanns-Ring 19, 4056, Basel, Switzerland. karl.gademann@uzh.ch.|Department Chemie, Universität Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. karl.gademann@uzh.ch.
authors.forename: Karl
authors.identifier: 0000-0003-3053-0689
authors.initials: K
authors.lastname: Gademann
mesh_terms: D000818:Animals; D033202:Anostraca / Q000187:drug effects*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D009842:Oligopeptides; C000624944:aeruginosin 828A
keywords: algal blooms; medicinal chemistry; natural products; total synthesis; toxicology