A5019466980- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and Catalytic Reactions
- Catalytic C–H Functionalization Methods
- Computational Drug Discovery Methods
- Malaria Research and Control
- Vitamin D Research Studies
- Synthesis and Biological Activity
- Nanocluster Synthesis and Applications
- Synthesis of β-Lactam Compounds
- Ubiquitin and proteasome pathways
- Regulation of Appetite and Obesity
- Gold and Silver Nanoparticles Synthesis and Applications
- Histone Deacetylase Inhibitors Research
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Adipokines, Inflammation, and Metabolic Diseases
- Radical Photochemical Reactions
- Chemical Synthesis and Analysis
- Advanced biosensing and bioanalysis techniques
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Degradation and Inhibitors
- Microbial Natural Products and Biosynthesis
- Cell Image Analysis Techniques
- Mosquito-borne diseases and control
Broad Institute
2016-2024
Harvard University
2017-2024
Frederick National Laboratory for Cancer Research
2012
National Cancer Institute
2012
Center for Cancer Research
2012
Cancer Center of Hawaii
2009
Cancer Research Center
2009
The development of new antimalarial therapeutics is necessary to address the increasing resistance current drugs. Bicyclic azetidines targeting Plasmodium falciparum phenylalanyl-tRNA synthetase comprise one promising class antimalarials, especially due their activities against three stages parasite's life cycle, but a lengthy synthetic route these compounds may affect feasibility delivering therapeutic agents within cost constraints Here, we report an efficient synthesis compound BRD3914...
In order to identify the most attractive starting points for drugs that can be used prevent malaria, a diverse chemical space comprising tens of thousands millions small molecules may need examined. Achieving this throughput necessitates development efficient ultra-high-throughput screening methods. Here, we report and evaluation luciferase-based phenotypic screen malaria exoerythrocytic-stage parasites optimized 1536-well format. This assay uses exoerythrocytic stage rodent parasite,...
Abstract Vitamin D deficiency and adipocytokines have been implicated in the etiology of aging-related diseases such as cancer, osteoporosis, cardiovascular system. The association between elevated parathyroid hormone (PTH) low 25-hydroxyvitamin (25-OH-VitD) plasma is used to define vitamin deficiency, yet their associated mechanistic pathways are unclear. Utilizing samples from women a previous intervention study, we measured 25-OH-VitD, leptin, adiponectin, PTH, lipid levels. We observed...
Target- and phenotype-agnostic assessments of biological activity have emerged as viable strategies for prioritizing scaffolds, structural features, synthetic pathways in screening sets, with the goal increasing performance diversity. Here, we describe synthesis a small library functionalized stereoisomeric azetidines its annotation by "cell painting," multiplexed, high-content imaging assay capable measuring many hundreds compound-induced changes cell morphology quantitative unbiased...
Dihydroorotate dehydrogenase (DHODH) is an enzyme necessary for pyrimidine biosynthesis in protozoan parasites of the genus Plasmodium, causative agents malaria. We recently reported identification novel compounds derived from diversity-oriented synthesis with activity multiple stages malaria parasite life cycle. Here, we report optimization a potent series antimalarial inhibitors consisting azetidine-2-carbonitriles, which had previously shown to target P. falciparum DHODH biochemical...
An efficient and stereospecific Pd-catalyzed protocol for the C–H arylation of pyroglutamic acid derivatives that uses 8-aminoquinoline as a directing group is described. The reaction was shown to proceed efficiently with variety aryl heteroaryl iodides bearing different functional groups, giving C3-arylated cis products in good high yields. Removal unit from these enables access synthetically useful trans acid-based building blocks.
Abstract Ubiquitin is a small, highly conserved protein that acts as posttranslational modification in eukaryotes. Ubiquitination of proteins frequently serves degradation signal, marking them for disposal by the proteasome. Here, we report novel small molecule from diversity-oriented synthesis library, BRD1732, directly ubiquitinated cells, resulting dramatic accumulation inactive ubiquitin monomers and polyubiquitin chains causing broad inhibition ubiquitin-proteasome system. BRD1732 its...