A5016177910- Reproductive tract infections research
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Syphilis Diagnosis and Treatment
- RNA Research and Splicing
- interferon and immune responses
- Viral Infections and Immunology Research
- Inhalation and Respiratory Drug Delivery
- Metal-Catalyzed Oxygenation Mechanisms
- Urticaria and Related Conditions
- Chemical Synthesis and Analysis
- Multicomponent Synthesis of Heterocycles
- Advanced Drug Delivery Systems
- Synthesis and Catalytic Reactions
- Viral Infectious Diseases and Gene Expression in Insects
- RNA regulation and disease
- Drug Solubulity and Delivery Systems
- Catalytic C–H Functionalization Methods
- RNA modifications and cancer
- Chemical Synthesis and Reactions
- Protein Degradation and Inhibitors
- Inflammatory mediators and NSAID effects
- Urinary Tract Infections Management
Yale University
2025
Carnegie Mellon University
2024
Chemical Genomics Centre
2020-2023
Max Planck Institute of Molecular Physiology
2020-2023
TU Dortmund University
2022-2023
Max Planck Institute of Molecular Cell Biology and Genetics
2023
University of Otago
2019-2022
Modulation of protein–RNA interaction (PRI) using small molecules is a promising strategy to develop therapeutics. LIN28 an RNA-binding protein that blocks the maturation tumor suppressor let-7 microRNAs. Herein, we performed fluorescence polarization-based screening and identified trisubstituted pyrrolinones as small-molecule inhibitors disrupting LIN28–let-7 interaction. The most potent compound C902 showed dose-dependent inhibition in EMSA validation assay, enhanced thermal stability cold...
Despite the promise of vastly expanding druggable genome, rational design RNA-targeting ligands remains challenging as it requires rapid identification hits and visualization resulting cocomplexes for guiding optimization. Here, we leveraged high-throughput screening, medicinal chemistry, structural biology to identify a de novo splicing inhibitor against large highly folded fungal group I intron. High-resolution cryoEM structures intron in different liganded states not only reveal molecular...
Abstract Targeting the protein−RNA interaction of LIN28 and let‐7 is a promising strategy for development novel anticancer therapeutics. However, limited number small‐molecule inhibitors disrupting LIN28‐ with potent efficacy are available. Herein, we developed LIN28‐inhibiting by targeting selective hotspot amino acids at binding interface small‐molecule‐based bifunctional conjugates. Starting from reported inhibitors, identified feasible linker‐attachment position after performing...
Herein, we describe the regioselective functionalization of unsymmetrical ketones using imine directing groups, Cu, and H2O2. The C–H hydroxylation substrate–ligands derived from 2-substituted benzophenones occurred exclusively at γ-position unsubstituted ring due to formation only one stereoisomer. Conversely, imines 4-substituted produced E/Z mixtures that upon reacting with Cu H2O2 led two γ-C–H products. Contrary our initial hypothesis, ratio products did not depend on isomers but...
Multicomponent Petasis reaction has been widely applied for the synthesis of functionalized amine building blocks and biologically active compounds. Employing primary aromatic amines that are not typical reactive substrates contributes to expand application scope reaction. In this study, we demonstrated 2-aminothiophenes using Gewald-reaction-derived as substrates, whose low reactivity in was overcome hexafluoro-2-propanol solvent a mild condition. The obtained products amenable further...
Nanoparticle drug delivery systems have emerged as a promising strategy for overcoming limitations of antimicrobial drugs such stability, bioavailability, and insufficient exposure to the hard-to-reach bacterial targets. Although size is vital colloidal feature nanoparticles that governs biological interactions, absence well-defined control technology has hampered investigation optimal nanoparticle targeting cells. Previously, we identified lead antichlamydial compound JO146 against high...
Small molecules targeting the ubiquitous latent ribonuclease (RNase L), which has limited sequence specificity toward single-stranded RNA substrates, hold great potential to be developed as broad-spectrum antiviral drugs by modulating RNase L-mediated innate immune responses. The recent development of proximity-inducing bifunctional molecules, described in strategy chimeras, demonstrated that small-molecule L activators can function essential L-recruiting component design for targeted...
High temperature requirement A (HtrA) serine proteases have emerged as a novel class of antibacterial target, which are crucial in protein quality control and involved the pathogenesis wide array bacterial infections. Previously, we demonstrated that HtrA Chlamydia is essential for survival, replication virulence. Here, report new series proline (P2)-modified inhibitors trachomatis (CtHtrA) developed by ring expansion Cγ-substitutions. The structure-based drug optimization process was guided...
High temperature requirement A (HtrA) serine proteases have emerged as a novel class of antibacterial target, which are crucial in protein quality control and involved the pathogenesis wide array bacterial infections. Previously, we demonstrated that HtrA Chlamydia is essential for survival, replication virulence. Here, report new series proline (P2)-modified inhibitors trachomatis (CtHtrA) developed by ring expansion Cγ-substitutions. The structure-based drug optimization process was guided...