ABSTRACT
The identification of natural product producer organisms remains a problem for both isolation and natural product classification. A concise screen is developed through fluorescent modification of a set of natural products that offer a common activity. Through real-time multicolor microscopy, the processing, storage, and effects of a natural product are rapidly screened at the level of the strain and individual organism.
Subject(s)
Biological Products/analysis , Biotechnology/methods , Animals , Biological Products/biosynthesis , Dinoflagellida/metabolism , Dinoflagellida/ultrastructure , Fluorescent Dyes/chemical synthesis , Sensitivity and SpecificityABSTRACT
A series of acyclic, truncated microcystin analogues, comprised of the dienic beta-amino acid (Adda) and up to four additional amino acids characteristic of the parent toxin, was synthesized and screened for activity as inhibitors of PP1 and PP2A. Despite a recent report to the contrary for a microcystin-derived tetrapeptide degradation product, none approaches the potency of microcystin itself.
Subject(s)
Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Phosphoprotein Phosphatases/antagonists & inhibitors , Bacterial Toxins , Inhibitory Concentration 50 , Isoenzymes , Marine Toxins , Microcystins , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Structure-Activity RelationshipABSTRACT
A series of greatly simplified microcystin analogues comprised only of Adda (the beta-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.
