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Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation
Published on: January 14, 2011
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Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships
Noemi Kedei1, Matthew B Kraft2, Gary E Keck2
1†Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-4255, United States.
Journal of Natural Products
|March 27, 2015
Summary
Neristatin 1, like bryostatin 1, antagonizes phorbol ester responses by activating protein kinase C (PKC). Its top half is key for this unique biological activity, requiring a functional PKC binding domain.
Area of Science:
- Biochemistry
- Pharmacology
- Molecular Biology
Background:
- Bryostatin 1, a marine natural product, activates protein kinase C (PKC) but antagonizes phorbol ester responses.
- The bottom half of bryostatin 1 confers PKC binding, while the top half is crucial for its unique biological activity.
Purpose of the Study:
- To investigate the biological activity of neristatin 1, a novel bryostatin analog.
- To determine the structural requirements for bryostatin 1-like activity, specifically its antagonism of phorbol ester responses.
Main Methods:
- Synthesis of neristatin 1, a molecule with a bryostatin 1-like top half and a distinct PKC-binding bottom half.
- Assessment of neristatin 1's biological activity on U937 promyelocytic leukemia cells, comparing it to bryostatin 1 and phorbol esters.
Main Results:
- Neristatin 1 exhibited bryostatin 1-like biological activity, antagonizing phorbol ester responses in U937 cells.
- The results indicate that the top half of bryostatin 1 is largely sufficient for bryostatin 1-like activity.
Conclusions:
- The top half of bryostatin 1 is critical for its unique biological activity in antagonizing phorbol ester responses.
- Neristatin 1's activity supports the conclusion that the top half confers bryostatin 1-like effects when paired with a suitable PKC binding domain.
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