A5042319227- RNA and protein synthesis mechanisms
- Microbial Natural Products and Biosynthesis
- Radical Photochemical Reactions
- Catalytic C–H Functionalization Methods
- Advanced biosensing and bioanalysis techniques
- Catalytic Cross-Coupling Reactions
- Phytochemical compounds biological activities
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Enzyme Catalysis and Immobilization
- Advanced Proteomics Techniques and Applications
- RNA Research and Splicing
- Carbohydrate Chemistry and Synthesis
- Fluorine in Organic Chemistry
- Synthetic Organic Chemistry Methods
- Machine Learning in Bioinformatics
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Genomics, phytochemicals, and oxidative stress
- Fungal Biology and Applications
- Mass Spectrometry Techniques and Applications
- Advanced Biosensing Techniques and Applications
- Enzyme Production and Characterization
- bioluminescence and chemiluminescence research
- RNA Interference and Gene Delivery
Merck & Co., Inc., Rahway, NJ, USA (United States)
2020-2023
Harvard University
2018
University of Michigan
2009-2013
Ann Arbor Center for Independent Living
2010
University of Notre Dame
2004-2005
A biocatalytic platform that employs the final two monomodular type I polyketide synthases of pikromycin pathway in vitro followed by direct appendage D-desosamine and C-H oxidation(s) vivo was developed applied toward synthesis a suite 12- 14-membered ring macrolide natural products. This methodology delivered both compound classes 13 steps (longest linear sequence) from commercially available (R)-Roche ester >10% overall yields.
Determination of target engagement for candidate drug molecules in the native cellular environment is a significant challenge discovery programs. The thermal shift assay (CETSA) has emerged as powerful tool determining compound through measurement changes to protein's stability upon ligand binding. Here, we present HiBiT (BiTSA) that deploys quantitative peptide tag determination using high throughput, plate-based luminescence readout. We demonstrate BiTSA can rapidly assess small molecule...
The 6-deoxyerythronolide B synthase (DEBS) and pikromycin (Pik) polyketide (PKS) are unique multifunctional enzyme systems that responsible for the biosynthesis of erythromycin 14-membered ring aglycones, respectively. Together, these natural product biosynthetic provide excellent platforms to examine fundamental structural catalytic elements govern assembly, processing, macrocyclization. In studies, native pentaketide intermediate DEBS was synthesized employed in vitro chemoenzymatic...
Although more than 98% of the human genome is noncoding, nearly all drugs on market target one about 700 disease-related proteins. However, an increasing number diseases are now being attributed to noncoding RNA and ability them would vastly expand chemical space for drug development. We recently devised a screening strategy based upon affinity-selection mass spectrometry succeeded in identifying bioactive compounds prototype, Xist. One such compound, termed X1, has drug-like properties...
2-Substituted pyridine, quinoline, isoquinoline, bipyridine, and 1,10-phenanthroline analogues of benzylic acetates undergo SmI2-promoted coupling with aldehydes ketones to afford (2-hydroxyalkyl)heteroaromatics.
1,10-Phenanthroline reacts with aldehydes and ketones in the presence of samarium diiodide to produce 2-(1-hydroxyalkyl)-1,10-phenanthrolines. The hydroxyalkyl substituent can be functionalized numerous ways or removed permit further ligand variation. carbonyl coupling reaction also repeated provide 2,9-disubstituted phenanthrolines. Taken together, these operations ready access a large number phenanthroline derivatives serve as libraries for catalyst exploration.
SUMMARY Apart from their antimicrobial properties, tetracyclines demonstrate clinically validated effects in the amelioration of pathological inflammation and human cancer. Delineation target(s) mechanism(s) responsible for these effects, however, has remained elusive. Here, employing quantitative mass spectrometry-based proteomics, we identified 80S ribosomes as targets Col-3 doxycycline. We then developed cell click selective crosslinking with RNA sequence profiling (icCL-Seq) to map...
Abstract Review: 65 refs.
Apart from their antimicrobial properties, tetracyclines demonstrate clinically validated effects in the amelioration of pathological inflammation and human cancer. Delineation target(s) mechanism(s) responsible for these effects, however, has remained elusive. Here, employing quantitative mass spectrometry-based proteomics, we identified 80S ribosomes as targets Col-3 doxycycline. We then developed cell click selective crosslinking with RNA sequence profiling (icCL-Seq) to map binding sites...
Abstract For see ChemInform in Full Text.
Abstract For see ChemInform in Full Text.