RESUMEN
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.
Asunto(s)
Productos Biológicos/análisis , Biotecnología/métodos , Animales , Productos Biológicos/biosíntesis , Dinoflagelados/metabolismo , Dinoflagelados/ultraestructura , Colorantes Fluorescentes/síntesis química , Sensibilidad y EspecificidadRESUMEN
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.
Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Toxinas Bacterianas , Concentración 50 Inhibidora , Isoenzimas , Toxinas Marinas , Microcistinas , Oligopéptidos/síntesis química , Oligopéptidos/farmacología , Relación Estructura-ActividadRESUMEN
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.