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Regioselective Cleavage of Thioether Linkages in Microcystin Conjugates
Author(s) -
Zemskov Ivan,
Kropp Heike M.,
Wittmann Valentin
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201601660
Subject(s) - thioether , nucleophile , chemistry , regioselectivity , reagent , cleavage (geology) , microcystin , moiety , covalent bond , cysteine , marine toxin , residue (chemistry) , derivatization , combinatorial chemistry , organic chemistry , cyanobacteria , biochemistry , high performance liquid chromatography , toxin , biology , enzyme , paleontology , genetics , fracture (geology) , bacteria , catalysis
Microcystins are cyanobacterial toxins that can be found in fresh and coastal waters during algal blooms. Microcystin contamination of water can cause severe poisoning of animals and humans. Quantification of these toxins in biological samples is complicated because a major proportion of microcystins is covalently linked to proteins through thioether bonds formed through a Michael‐type addition of cysteine residues of proteins to an N ‐methyldehydroalanine residue in the microcystins. We investigated chemical methods that can be used to cleave such thioether bonds by means of an elimination reaction that leaves the microcystin backbone intact for subsequent analysis. The known reagent O ‐mesitylenesulfonylhydroxylamine (MSH) led to regioselective thioether cleavage, but a large excess of reagent was needed, thus making purification challenging. An unexpected side reaction observed during the investigation of the base‐induced elimination inspired us to develop a new thioether‐cleavage methodology based on the addition of propargylamine as a nucleophile that can trap the elimination product. This methodology could be successfully applied to the quantitative cleavage of a microcystin‐LF–glutathione conjugate. The alkyne moiety introduced by this procedure offers the possibility for further reactions with azides by using click chemistry, which might be useful for the derivatization or isolation of microcystins.