Publications by authors named "B I Posner"
The kinase-like NiRAN domain of nsp12 in SARS-CoV-2 catalyzes the formation of the 5' RNA cap structure. This activity is required for viral replication, offering a new target for the development of antivirals. Here, we develop a high-throughput assay to screen for small molecule inhibitors targeting the SARS-CoV-2 NiRAN domain.
View Article and Find Full Text PDFWe describe the development of a unified synthetic strategy for the preparation of all known 5/5-spirocyclic spiroindimicin (SPM) alkaloids, namely spiroindimicins B-G. The present synthetic route relies on four fundamental transformations: Grignard-based fragment coupling between halogenated pyrrolemetal and isatin partners, Suzuki coupling to generate a triaryl scaffold encompassing all requisite skeletal atoms of the natural products, Lewis acid-mediated spirocyclization to construct the 5/5-spirocyclic core, and chemoselective lactam reduction. The developed syntheses are step-economic (6-7 steps from commercial materials), scalable, and amenable to analogue synthesis.
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- Acute myeloid leukemia (AML) is the most common type of leukemia in adults and is hard to treat because everyone's disease can be different.
- The main treatment has been the same for a long time, but researchers are studying how different cancer drugs work together to find better options.
- Some newer drugs showed good results when used with others, while an older drug caused problems when mixed with different medicines, making it clear that treatment success can depend on the specific type of AML.
Article Synopsis
- Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) is a form of retinal degeneration linked to a specific genetic mutation in the fibulin-3 protein, similar to age-related macular degeneration (AMD).
- Researchers developed a method to track fibulin-3 levels in retinal cells and found that the GSK3 inhibitor CHIR99021 effectively reduced its production and altered cell behavior.
- In tests on mice with the ML/DHRD mutation, CHIR treatment significantly decreased harmful structures associated with the disease, suggesting its potential for treating AMD and similar retinal disorders.
Article Synopsis
- - Heterozygous mutations in the GRN gene are a key cause of hereditary frontotemporal dementia, but the underlying mechanisms and treatments are not well understood.
- - The proposed strategy involves using small molecules to enhance GRN expression from the remaining good GRN allele, aiming to normalize progranulin levels in the brain.
- - Research identifies new small molecules that effectively increase progranulin levels in human cells and Grn mouse brains, potentially reversing symptoms associated with frontotemporal dementia and paving the way for future drug development.