David Berkowitz

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Etoposide is one of the most successful chemotherapeutic agents used for the treatment of human cancers. The drug kills cells by inhibiting the ability of topoisomerase II to ligate nucleic acids that it cleaves during the double-stranded DNA passage reaction. Etoposide is composed of a polycyclic ring system (rings A-D), a glycosidic moiety at the C4(More)
Hyperthermophilic archaea are of great interest in evolutionary microbiology, owing to their ability to withstand high temperatures and often extremes of pressure, pH, and salinity. Enzymes from these organisms 1 may offer particular opportunities for asymmetric synthesis, complementary to approaches with mesophilic enzymes, 2 or those involving enzyme 3(More)
The use of NADH- and NADPH-dependent ketoreductases to access enantioenriched pharmaceutical building blocks is reported. Seven structurally diverse synthons are obtained, including those for atomoxetine (KRED 132), talampanel (RS1-ADH and CPADH), Dolastatin (KRED 132), and fluoxetine (KRED 108/132). Ethanol may be used as stoichiometric reductant,(More)
The glmS riboswitch is unique among gene-regulating riboswitches and catalytic RNAs. This is because its own metabolite, glucosamine-6-phosphate (GlcN6P), binds to the riboswitch and catalytically participates in the RNA self-cleavage reaction, thereby providing a novel negative feedback mechanism. Given that a number of pathogens harbor the glmS(More)
This study introduces new methods of screening for and tuning chiral space and in so doing identifies a promising set of chiral ligands for asymmetric synthesis. The carbafructopyranosyl-1,2-diamine(s) and salens constructed therefrom are particularly compelling. It is shown that by removing the native anomeric effect in this ligand family, one can tune(More)
The gaseous neuromodulator H2S is associated with neuronal cell death pursuant to cerebral ischemia. As cystathionine β-synthase (CBS) is the primary mediator of H2S biogenesis in the brain, it has emerged as a potential target for the treatment of stroke. Herein, a "zipped" approach by alkene cross-metathesis into CBS inhibitor candidate synthesis is(More)
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