Publications by authors named "O Wiest"
The synthesis of photocaged substrates of the biologically important enzyme HMG-CoA reductase is reported. HMG-CoA bearing a -hydroxyphenacyl (pHP) photocage moiety was synthesized in an overall yield of 14% over seven steps in addition to caged forms of mevalonate and mevaldehyde. The absorption maximum and quantum yield for the decaging of the photocaged compounds are dependent on pH with a λ of 330 nm and a ϕ of 5%, respectively, at pH 9.
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- Scientists are looking for medicines that can help fix problems caused by bad versions of proteins in diseases, especially for Niemann-Pick type C1 disease, which affects how cholesterol moves in cells and can cause serious health issues.
- They studied special human brain cells with different types of NPC1 mutations (the bad protein) to find small drugs that could help the protein work better.
- They found a drug called mo56-hydroxycholesterol that helps these mutant proteins and created mice with a common mutation to better understand the disease and test the drug's effects.
Machine learning-driven computer-aided synthesis planning (CASP) tools have become important tools for idea generation in the design of complex molecule synthesis but do not adequately address the stereochemical features of the target compounds. A novel approach to automated extraction of templates used in CASP that includes stereochemical information included in the US Patent and Trademark Office (USPTO) and an internal AstraZeneca database containing reactions from Reaxys, Pistachio, and AstraZeneca electronic lab notebooks is implemented in the freely available AiZynthFinder software. Three hundred sixty-seven templates covering reagent- and substrate-controlled as well as stereospecific reactions were extracted from the USPTO, while 20,724 templates were from the AstraZeneca database.
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- Staphylococcus aureus can invade bone structures and cause infections like osteomyelitis, with the cell wall protein PBP4 being vital for this process.
- Deleting the pbp4 gene prevents the bacteria from invading bone networks and causing disease in mice.
- Research has identified a chemical, phenyl-urea 1, that targets PBP4, and further studies on related compounds have shown potential for better binding and effectiveness against antibiotic resistance.
The application of machine learning models to the prediction of reaction outcomes currently needs large and/or highly featurized data sets. We show that a chemistry-aware model, NERF, which mimics the bonding changes that occur during reactions, allows for highly accurate predictions of the outcomes of Diels-Alder reactions using a relatively small training set, with no pretraining and no additional features. We establish a diverse data set of 9537 intramolecular, hetero-, aromatic, and inverse electron demand Diels-Alder reactions.
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