[reaction: see text] A new approach to the synthesis of the C ring subunit of known and potential bryostatin analogues is described. The convergent approach, illustrated above, requires fewer steps and offers greater flexibility in rapidly accessing diverse C ring analogues.
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http://dx.doi.org/10.1021/ol0355332 | DOI Listing |
Front Cell Neurosci
May 2024
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Protein kinase C (PKC) plays a key role in modulating the activities of the innate immune cells of the central nervous system (CNS). A delicate balance between pro-inflammatory and regenerative activities by microglia and CNS-associated macrophages is necessary for the proper functioning of the CNS. Thus, a maladaptive activation of these CNS innate immune cells results in neurodegeneration and demyelination associated with various neurologic disorders, such as multiple sclerosis (MS) and Alzheimer's disease.
View Article and Find Full Text PDFPathog Immun
April 2024
Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California.
Background: Latency reversing agents (LRAs) such as protein kinase C (PKC) modulators can reduce rebound-competent HIV reservoirs in small animal models. Furthermore, administration of natural killer (NK) cells following LRA treatment improves this reservoir reduction. It is currently unknown why the combination of a PKC modulator and NK cells is so potent and whether exposure to PKC modulators may augment NK cell function in some way.
View Article and Find Full Text PDFbioRxiv
February 2024
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Protein kinase C (PKC) plays a key role in modulating the activities of the innate immune cells of the central nervous system (CNS). A delicate balance between pro-inflammatory and regenerative activities by microglia and CNS-associated macrophages is necessary for the proper functioning of the CNS. Thus, a maladaptive activation of these CNS innate immune cells results in neurodegeneration and demyelination associated with various neurologic disorders, such as multiple sclerosis (MS) and Alzheimer's disease.
View Article and Find Full Text PDFBioorg Med Chem Lett
January 2024
Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60660, USA. Electronic address:
Small molecule activators of protein kinase C (PKC) have traditionally been classified as either tumor promoters or suppressors. Although bryostatin 1 has well established anti-cancer activity, most natural products that target the PKC regulator domain exhibit tumor promotion properties. In this study, we examine a focused library of indolactam analogues in cell-based assays to establish the structural features of the scaffold that enhance bryostatin 1-like activity.
View Article and Find Full Text PDFVirology
April 2023
Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, CA, 92697, USA; Department of Medicine (Division of Infectious Diseases), School of Medicine, University of California Irvine, CA, 92697, USA. Electronic address:
HIV can establish a long-lived latent infection in cells harboring integrated non-expressing proviruses. Latency reversing agents (LRAs), including protein kinase C (PKC) modulators, can induce expression of latent HIV, thereby reducing the latent reservoir in animal models. However, PKC modulators such as bryostatin-1 also cause cytokine upregulation in peripheral blood mononuclear cells (PBMCs), including cytokines that might independently reverse HIV latency.
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