Remarkable stereospecific conjugate additions to the Hsp90 inhibitor celastrol

Lada Klaić, Paul C. Trippier, Rama K. Mishra, Richard I. Morimoto, Richard B. Silverman

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)19634-19637
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number49
DOIs
StatePublished - Dec 14 2011
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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