Microcystin analogues comprised only of adda and a single additional amino acid retain moderate activity as PP1/PP2A inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 17; pp. 2907 - 2911
• Main Authors: Gulledge, Brian M, Aggen, James B, Eng, Hugo, Sweimeh, Khuloud, Chamberlin, A.Richard
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-09-2003; Elsevier
• Subjects: Amino Acids - chemistry; Bacterial Toxins; Bacteriology; Biological and medical sciences; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Inhibitory Concentration 50; Isoenzymes - antagonists & inhibitors; Microbiology; Microcystins; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacology; Phosphoprotein Phosphatases - antagonists & inhibitors; Structure-Activity Relationship; Peptides; Structure activity relation; Enzyme; Phosphoprotein phosphatase; Phosphoric monoester hydrolases; Dipeptides; Enzyme inhibitor; Hydrolases; Esterases; Peptide synthesis; Chemical synthesis; In vitro
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00588-2

A series of greatly simplified microcystin analogues comprised only of Adda (the β-amino acid common to the microcystins, nodularins, and motuporin,) and a single additional amino acid residue was synthesized and screened for inhibition of the protein phosphatases 1 and 2A. Several of the analogues were shown to be mid-nanomolar inhibitors of the enzymes.
A series of greatly simplified microcystin analogues was synthesized and screened for inhibition of the protein phosphatases 1 and 2A, with several of the analogues shown to be mid-nanomolar inhibitors of the enzymes.