N-Formyl-7-amino-11-cycloamphilectene, a marine sponge metabolite, binds to tubulin and modulates microtubule depolymerization.
Mol Biosyst
; 10(4): 862-7, 2014 Apr.
Article
en En
| MEDLINE
| ID: mdl-24493364
ABSTRACT
The importance of protein-small molecule interaction in drug discovery, medicinal chemistry and biology has driven the development of new analytical methods to disclose the whole interactome of bioactive compounds. To accelerate targets discovery of N-formyl-7-amino-11-cycloamphilectene (CALe), a marine bioactive diterpene isolated from the Vanuatu sponge Axinella sp., a chemoproteomic-based approach has been successfully developed. CALe is a potent anti-inflammatory agent, modulating NO and prostaglandin E2 overproduction by dual inhibition of the enhanced inducible NO synthase expression and cyclo-oxygenase-2 activity, without any evidence of cytotoxic effects. In this paper, several isoforms of tubulin have been identified as CALe off-targets by chemical proteomics combined with bio-physical orthogonal approaches. In the following biological analysis of its cellular effect, CALe was found to protect microtubules against the colcemid depolymerizing effect.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tubulina (Proteína)
/
Diterpenos
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Óxido Nítrico Sintasa de Tipo II
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Inhibidores de la Ciclooxigenasa 2
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Microtúbulos
Límite:
Animals
Idioma:
En
Revista:
Mol Biosyst
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Italia