A5044018083- Advanced biosensing and bioanalysis techniques
- Advanced Proteomics Techniques and Applications
- Estrogen and related hormone effects
- Click Chemistry and Applications
- Retinoids in leukemia and cellular processes
- Advanced Biosensing Techniques and Applications
- Conducting polymers and applications
- Enzyme function and inhibition
- Menopause: Health Impacts and Treatments
- Liver physiology and pathology
- Microbial Natural Products and Biosynthesis
- Immunodeficiency and Autoimmune Disorders
- Biochemical and Molecular Research
- PARP inhibition in cancer therapy
- Whipple's Disease and Interleukins
- Carbohydrate Chemistry and Synthesis
- PI3K/AKT/mTOR signaling in cancer
- Semiconductor materials and devices
- Psoriasis: Treatment and Pathogenesis
- Integrated Circuits and Semiconductor Failure Analysis
- Organic Electronics and Photovoltaics
- Chemical Synthesis and Analysis
- Phagocytosis and Immune Regulation
- Luminescence and Fluorescent Materials
Palomar Health
2024
Center for Cancer Research
2016-2017
Purdue University West Lafayette
2016-2017
University of Toledo
2012-2013
South Dakota School of Mines and Technology
2010
Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition using antibodies proven as an effective treatment. Oral anti-IL17 therapies are attractive alternative option, several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery a novel class inhibitors, identified via DNA-encoded chemical library screen, their subsequent optimization to provide in vivo efficacious inhibitors. These new protein–protein...
DNA-encoded chemical library (DEL) technology provides a time- and cost-efficient method to simultaneously screen billions of compounds for their affinity protein target interest. Here we report its use identify novel series inhibitors the thioesterase activity polyketide synthase 13 (Pks13) from Mycobacterium tuberculosis (Mtb). We present three chemically distinct along with enzymatic Mtb whole cell potency, measure on-target in cells, crystal structures inhibitor-enzyme complexes...
Abstract A sensing approach is applied to encode quantitative enzymatic activity information into DNA sequence populations. The method utilizes DNA‐linked peptide substrates as probes. Signal detection involves chemical manipulation of a probe population downstream sample exposure and application purifying, selective pressure for enzyme products. Selection‐induced changes in abundance indicate activity. protein kinase, protease, farnesyltransferase activities demonstrated. assays were...
Mer is a member of the TAM (Tyro3, Axl, Mer) kinase family that has been associated with cancer progression, metastasis, and drug resistance. Their essential function in immune homeostasis prompted an interest their role as modulators antitumor response tumor microenvironment. Here we illustrate outcomes extensive lead-generation campaign for identification inhibitors, focusing on results from concurrent, orthogonal high-throughput screening approaches. Data mining, HT (high-throughput),...
The c-MET receptor tyrosine kinase has received considerable attention as a cancer drug target yet there remains need for inhibitors which are selective and able to emerging drug-resistant mutants. We report here the discovery, by screening DNA-encoded chemical library, of highly inhibitor was shown X-ray crystallography bind in an unprecedented manner. These results represent novel mode inhibiting with small molecule may provide route targeting forms whilst avoiding potential toxicity...
Here, we describe an immunoassay approach for the detection of enzyme activity by quantitative PCR (qPCR) or parallel DNA sequencing which relies on activity-based probes linked to barcoding DNAs. We demonstrate this technique in serine hydrolase activities using a fluorophosphonate-oligonucleotide conjugate.
Abstract A sensing approach is applied to encode quantitative enzymatic activity information into DNA sequence populations. The method utilizes DNA‐linked peptide substrates as probes. Signal detection involves chemical manipulation of a probe population downstream sample exposure and application purifying, selective pressure for enzyme products. Selection‐induced changes in abundance indicate activity. protein kinase, protease, farnesyltransferase activities demonstrated. assays were...
Inhibition of poly (ADP-ribose) polymerase-1 (PARP1), a DNA repair enzyme, has proven to be successful strategy for the treatment various cancers. With appropriate selection conditions and protein design, DNA-encoded library (DEL) technology provides powerful avenue identify small molecules with desired mechanism action towards target interest. However, DNA-binding proteins, such as PARP1, can challenging targets DEL screening due non-specific protein-DNA interactions. To overcome this, we...