Design, synthesis, and biological evaluation of a potent, PKC selective, B-ring analog of bryostatin

Org Lett. 2006 Apr 27;8(9):1893-6. doi: 10.1021/ol060457z.

Abstract

[structure: see text] The first member of a new class of five-membered B-ring analogs of bryostatin has been synthesized and tested for its ability to bind and translocate protein kinase C (PKC). This synthesis extends the utility of our previously introduced macrotransacetalization strategy to the formation of five-membered dioxolane B-ring analogs. This analog exhibits potent, single-digit nanomolar affinity to PKC and selectively translocates novel PKC isozymes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bryostatins
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry*
  • Macrolides / pharmacology
  • Molecular Structure
  • Protein Kinase C / chemistry
  • Protein Kinase C / metabolism*
  • Structure-Activity Relationship

Substances

  • Bryostatins
  • Macrolides
  • bryostatin 1
  • Protein Kinase C