Functional chromatography reveals three natural products that target the same protein with distinct mechanisms of action.
Chembiochem
; 15(14): 2125-31, 2014 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-25125376
ABSTRACT
Access to lead compounds with defined molecular targets continues to be a barrier to the translation of natural product resources. As a solution, we developed a system that uses discrete, recombinant proteins as the vehicles for natural product isolation. Here, we describe the use of this functional chromatographic method to identify natural products that bind to the AAA+ chaperone, p97, a promising cancer target. Application of this method to a panel of fungal and plant extracts identified rheoemodin, 1-hydroxydehydroherbarin, and phomapyrrolidone A as distinct p97 modulators. Excitingly, each of these molecules displayed a unique mechanism of p97 modulation. This discovery provides strong support for the application of functional chromatography to the discovery of protein modulators that would likely escape traditional high-throughput or phenotypic screening platforms.
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Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
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Proteínas Nucleares
/
Adenosina Trifosfatases
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article