Role of the A-ring of bryostatin analogues in PKC binding: synthesis and initial biological evaluation of new A-ring-modified bryologs

Org Lett. 2005 May 12;7(10):1995-8. doi: 10.1021/ol0504650.

Abstract

The syntheses of three newly designed bryostatin analogues are reported. These simplified analogues, which lack the A-ring present in the natural product but possess differing groups at C9, were obtained using a divergent approach from a common intermediate. All three analogues exhibit potent, single-digit nanomolar affinity to protein kinase C.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Brain / enzymology
  • Bryostatins
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry*
  • Macrolides / pharmacology
  • Molecular Structure
  • Protein Kinase C / chemistry*
  • Protein Kinase C / metabolism
  • Rats
  • Structure-Activity Relationship

Substances

  • Bryostatins
  • Macrolides
  • bryostatin 1
  • Protein Kinase C