Remarkable stereospecific conjugate additions to the Hsp90 inhibitor celastrol.
J Am Chem Soc
; 133(49): 19634-7, 2011 Dec 14.
Article
em En
| MEDLINE
| ID: mdl-22087583
ABSTRACT
Celastrol, an important natural product and Hsp90 inhibitor with a wide range of biological and medical activities and broad use as a biological probe, acts by an as yet undetermined mode of action. It is known to undergo Michael additions with biological sulfur nucleophiles. Here it is demonstrated that nucleophiles add to the pharmacophore of celastrol in a remarkable stereospecific manner. Extensive characterization of the addition products has been obtained using NMR spectrometry, nuclear Overhauser effects, and density functional theory to determine facial selectivity and gain insight into the orbital interactions of the reactive centers. This stereospecificity of celastrol may be important to its protein target selectivity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triterpenos
/
Proteínas de Choque Térmico HSP90
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos