A5005736215- Synthetic Organic Chemistry Methods
- Catalytic Alkyne Reactions
- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Reactions
- HIV/AIDS drug development and treatment
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Click Chemistry and Applications
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Cyclopropane Reaction Mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Traditional and Medicinal Uses of Annonaceae
- Radiation Effects in Electronics
- Synthesis of Indole Derivatives
- Cancer, Hypoxia, and Metabolism
- VLSI and Analog Circuit Testing
- Asymmetric Hydrogenation and Catalysis
- Biochemical and Structural Characterization
- Heat Transfer and Optimization
- Glioma Diagnosis and Treatment
National Institute of Diabetes and Digestive and Kidney Diseases
2018-2024
National Institutes of Health
2018-2024
University of North Carolina at Chapel Hill
2014-2024
Shanghai Xuhui Central Hospital
2024
Synthetic Biologics (United States)
2022
Tsinghua University
2005-2021
Institute of Bioorganic Chemistry
2020
Beijing Fengtai Hospital
2015
Alberta Glycomics Centre
2010-2013
University of Alberta
2010-2013
Boronic acid catalysis (BAC) was applied to the 1,3-transposition of allylic alcohols and related Meyer–Schuster rearrangement propargylic using highly electron deficient polyfluoroarylboronic acids as catalysts under mild metal-free conditions. A wide range synthetically useful products are formed in E : Z selectivities superior that metal-catalyzed methods. mechanism is proposed involving partial or full ionization into an (or propargylic) carbocation, additional possibilities for...
Herein, the concept of boronic acid catalysis (BAC) for activation unsaturated carboxylic acids is applied in several classic dipolar [3+2] cycloadditions involving azides, nitrile oxides, and nitrones as partners. These can be used to produce pharmaceutically interesting, small heterocyclic products, such triazoles, isoxazoles, isoxazolidines. cycloadducts are formed directly include a free functionality that employed further transformations, thereby avoiding prior masking or...
BAC to the future: Boronic acid catalysis (BAC) was applied direct activation of alcohols leading preparation carbocycles (see scheme), benzofurans, tetrahydrofurans, pyrrolidines, pyrans, piperidines, and various polycyclic compounds. The reactions proceed under mild conditions that circumvent use reactive leaving groups like halides. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They...
An enantioselective ring-expanding cycloisomerization of 1,5-enynes bearing a cyclopropylidene moiety has been developed. This methodology provides new approach to bicyclo[4.2.0]octanes, structural motif present in many biologically active natural products.
Abstract Isocitrate dehydrogenase 1 and 2 (IDH1 IDH2) are key metabolic enzymes that mutated in a variety of cancers to confer gain-of-function activity resulting the accumulation an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation 2-HG can result epigenetic dysregulation block cellular differentiation, suggesting these mutations play role neoplasia. Based on its potential as cancer target, number small molecule inhibitors have been developed specifically inhibit mutant forms IDH...
The evolution of drug resistance to many antimalarial drugs in the lethal strain malaria (Plasmodium falciparum) has been a great concern over past 50 years. Among these drugs, artemisinin become less effective for treating malaria. Indeed, several P. falciparum variants have resistant this drug, as elucidated by specific mutations pfK13 gene. This study presents development diagnostic kit detection common point mutation gene falciparum, namely, C580Y mutation. FIT-PNAs (forced-intercalation...
MERTK and AXL are members of the TAM (TYRO3, AXL, MERTK) family receptor tyrosine kinases that aberrantly expressed have been implicated as therapeutic targets in a wide variety human tumors. Dual inhibition could provide antitumor action mediated by both direct tumor cell killing modulation innate immune response some tumors such nonsmall lung cancer. We utilized our knowledge inhibitors structure-based drug design approach to discover novel class macrocyclic dual MERTK/AXL inhibitors. The...
Significance Type 2 diabetes (T2D) has emerged as a major threat to human health worldwide. In T2D, pancreatic β cells are unable release sufficient amounts of insulin maintain physiological blood glucose levels. Acetylcholine (ACh) stimulates from mouse and by activating cell surface receptor known M 3 muscarinic ACh (M3R). the present study, we show that drug binds an allosteric site on M3R (a distinct ACh-binding site) greatly enhances ACh-induced, M3R-mediated improves homeostasis in...
We report a series of synthetic, nucleic acid mimics with highly customizable thermodynamic binding to DNA. Incorporation helix-promoting cyclopentanes into peptide acids (PNAs) increases the melting temperatures (Tm) PNA+DNA duplexes by approximately +5°C per cyclopentane. Sequential addition allows Tm PNA + DNA be systematically fine-tuned from +5 +50°C compared unmodified PNA. Containing only nine nucleobases and an equal number cyclopentanes, cpPNA-9 binds complementary around 90°C....
Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are oncogenic for a number of malignancies, primarily low-grade gliomas and acute myeloid leukemia. We report medicinal chemistry campaign around 7,7-dimethyl-7,8-dihydro-2H-1λ2-quinoline-2,5(6H)-dione screening hit against the R132H R132C mutant forms (IDH1). Systematic SAR efforts produced series potent pyrid-2-one mIDH1 inhibitors, including atropisomer (+)-119 (NCATS-SM5637, NSC 791985). In an engineered mIDH1-U87-xenograft mouse...
Abstract An unprecedented gold‐catalyzed diastereoselective cycloisomerization of 1,6‐diynes bearing an alkylidene cyclopropane moiety has been developed. This methodology enables rapid access to a variety 1,2‐trimethylenenorbornanes, which are important building blocks in the preparations abiotic and sesquiterpene core structures.
Das Konzept der Boronsäurekatalyse (BAC) wurde für die direkte Aktivierung von Alkoholen zur Bildung Carbocyclen (siehe Schema), Benzofuranen, Tetrahydrofuranen, Pyrrolidinen, Pyranen, Piperidinen und verschiedenen polycyclischen Verbindungen genutzt. Die Reaktionen verlaufen unter milden Bedingungen umgehen den Einsatz reaktiver Abgangsgruppen wie Halogeniden.
•Partial endothelial-to-mesenchymal transition (EndMT) helps create new blood vessels and repair tissues after a lack of flow.•GTF2H4 works together with ERCC3 to encourage partial EndMT through the NCOA3/NF-κB/Snail pathway.•Targeting endothelial GTF2H4 could be hopeful treatment for diseases caused by insufficient supply. Partial is an intermediate phenotype observed in cells (ECs) undergoing toward mesenchymal state support neovascularization during (patho)physiological angiogenesis....
Cyclopentane-modified PNA monomers surrounding BisQ (surrogate base) significantly increase the sensitivity and selectivity for RNA detection by FIT-PNAs.
Selective incorporation of conformational constraints into thyclotides can be used to modulate their binding complementary oligonucleotides, increase polarity, and optimize uptake HCT116 cells without assistance from moieties known promote cell uptake. The X-ray structure biophysical studies a thyclotide-DNA duplex reveal that tetrahydrofurans an aegPNA backbone promotes helical conformation enhances DNA RNA. the allows polarity increased incrementally so optimized. enhanced binding,...
Abstract Peptide nucleic acids (PNAs) are promising therapeutic molecules for gene modulation; however, they suffer from poor cell uptake. Delivery of PNAs into cells requires conjugation the PNA to another large molecule, typically a cell-penetrating peptide or nanoparticle. In this study, we describe new PNA-based molecule with cyclic tetrahydrofuran (THF) backbone modifications that in some cases considerably improve We refer these THF-PNA oligomers as thyclotides. With THF groups at...
An efficient synthesis of Fmoc-protected (S,S)-trans-cyclopentane PNA (tcypPNA) monomers starting from mono-Boc-protected (S,S)-1,2-cyclopentanediamine is reported. A general synthetic strategy was developed so that tcypPNA with each nucleobase can be made in sufficient quantity and purity for use solid-phase peptide (SPPS). The newly synthesized were then successfully incorporated into 10-residue oligomers using standard Fmoc chemistry SPPS. different tcypPNAs allow positions the sequence...
Ginsenoside-Rg5, which is derived from high temperature-processed ginseng, exhibits beneficial health effects. In the present study, ginsenoside-Rg5 was directly and rapidly prepared through extraction of ginseng fibrous root powder (GFRP) at atmospheric pressure. The results showed that highest yield (3.79%) obtained under optimal conditions (extraction temperature 85 °C, acid concentration 0.06 mol/L, sample to solvent ratio 1:55 g/mL ethanol 95% after 4 h). current method integrates...