HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships.

Abstract
Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain.
AuthorsNoemi Kedei, Matthew B Kraft, Gary E Keck, Cherry L Herald, Noeleen Melody, George R Pettit, Peter M Blumberg
JournalJournal of natural products (J Nat Prod) Vol. 78 Issue 4 Pg. 896-900 (Apr 24 2015) ISSN: 1520-6025 [Electronic] United States
PMID25808573 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Bryostatins
  • Phorbol Esters
  • neristatin 1
  • bryostatin 1
  • Protein Kinase C
Topics
  • Animals
  • Bryostatins (chemistry)
  • Bryozoa (chemistry)
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Phorbol Esters
  • Protein Kinase C (drug effects, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: