A5014628793- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Protein Degradation and Inhibitors
- Mycobacterium research and diagnosis
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- Tuberculosis Research and Epidemiology
- Cell Image Analysis Techniques
- Microbial Natural Products and Biosynthesis
- Biotin and Related Studies
- Receptor Mechanisms and Signaling
- Histone Deacetylase Inhibitors Research
- Advanced biosensing and bioanalysis techniques
- bioluminescence and chemiluminescence research
- Antibiotic Resistance in Bacteria
- Escherichia coli research studies
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Biosensors and Analytical Detection
- Transgenic Plants and Applications
- Gut microbiota and health
Merck & Co., Inc., Rahway, NJ, USA (United States)
2019-2023
Stanford University
2017-2022
University of California, Berkeley
2016-2018
California Institute of Technology
2015
Many disease pathologies can be understood through the elucidation of localized biomolecular networks, or microenvironments. To this end, enzymatic proximity labeling platforms are broadly applied for mapping wider spatial relationships in subcellular architectures. However, technologies that map microenvironments with higher precision have long been sought. Here, we describe a microenvironment-mapping platform exploits photocatalytic carbene generation to selectively identify...
Significance The spread of multidrug-resistant infections demands antibiotic development. Although new antibiotics targeting gram-positive bacteria have been developed, it has more than 50 y since a class gram-negative approved for clinical use. strong outer membrane permeability barrier makes difficult compounds to reach intracellular targets, contributing greatly the lack this microbes. Here, we describe compound, MRL-494, that inhibits assembly proteins into by an essential member...
Modern proximity labeling techniques have enabled significant advances in understanding biomolecular interactions. However, current tools primarily utilize activation modes that are incompatible with complex biological environments, limiting our ability to interrogate cell- and tissue-level microenvironments animal models. Here, we report μMap-Red, a platform uses red-light-excited Sn
A solvatochromic trehalose dye conjugate allows the fast and specific detection of Mycobacterium tuberculosis in sputum samples.
Mycobacteria are endowed with a highly impermeable mycomembrane that confers intrinsic resistance to many antibiotics. Several unique glycolipids have been isolated and structurally characterized, but the underlying organization dynamics of within cell envelope remain poorly understood. We report here study was enabled by trehalose-fluorophore conjugates capable labeling trehalose in live actinomycetes. identified fluorescein-trehalose analogues metabolically incorporated into mycolates...
Over half of new therapeutic approaches fail in clinical trials due to a lack target validation. As such, the development methods improve and accelerate identification cellular targets, broadly known as ID, remains fundamental goal drug discovery. While advances sequencing mass spectrometry technologies have revolutionized ID recent decades, corresponding chemical-based not changed over 50 y. Consigned outdated stoichiometric activation modes, modern campaigns are regularly confounded by...
The characterization of ligand binding modes is a crucial step in the drug discovery process and especially important campaigns arising from phenotypic screening, where protein target mode are unknown at outset. Elucidation regions typically achieved by X-ray crystallography or photoaffinity labeling (PAL) approaches; yet, these methods present significant challenges. mainstay technique that has revolutionized discovery, but many cases structural challenging impossible. PAL also enabled site...
Several important human pathogens are represented in the Corynebacterineae suborder, including Mycobacterium tuberculosis and Corynebacterium diphtheriae. These bacteria surrounded by a multilayered cell envelope composed of cytoplasmic membrane, peptidoglycan (PG) wall, second polysaccharide layer called arabinogalactan (AG), finally an outer membrane-like made mycolic acids. anti-tuberculosis drugs target biogenesis this complex envelope, but their efficacy is declining due to resistance....
Abstract We describe a general synthetic strategy for developing high‐affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope interest is synthesized as polypeptide, with detection biotin tag and strategically placed azide (or alkyne) presenting amino acid. This (SynEp) incubated library complementary alkyne or peptides. Library elements that bind the SynEp in correct orientation undergo Huisgen cycloaddition, are covalently linked to SynEp. Hit...
Front-line tuberculosis (TB) drugs have been characterized extensively in vitro and vivo with respect to gene expression cell viability. However, little work has devoted understanding their effects on the physiology of envelope, one main targets this clinical regimen. Herein, we use metabolic labeling methods visualize TB envelope dynamics mycobacterial species. We developed a new fluorophore-trehalose conjugate trehalose monomycolates mycomembrane using super-resolution microscopy. also...
Abstract The identification of cellular targets that can be exploited for therapeutic benefit, broadly known as target ID, remains a fundamental goal in drug discovery. In recent years, the application new chemical and biological technologies accelerate ID has become commonplace within discovery programs, complete understanding how molecules react environment lead to increased binding selectivity, improved safety profiles, clinical efficacy. Established approaches using photoaffinity...
Abstract We describe a general synthetic strategy for developing high‐affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope interest is synthesized as polypeptide, with detection biotin tag and strategically placed azide (or alkyne) presenting amino acid. This (SynEp) incubated library complementary alkyne or peptides. Library elements that bind the SynEp in correct orientation undergo Huisgen cycloaddition, are covalently linked to SynEp. Hit...
Vaccine scaffolds and carrier proteins increase the immunogenicity of subunit vaccines. Here, we developed, characterized, demonstrated efficacy a novel microparticle vaccine scaffold comprised bacterial peptidoglycan (PGN), isolated as an entire sacculi. The PGN microparticles contain bio-orthogonal chemical handles allowing for site-specific attachment immunogens. We first evaluated purification, integrity, derived from variety species. then optimized modification conditions;...
Abstract Front‐line tuberculosis (TB) drugs have been characterized extensively in vitro and vivo with respect to gene expression cell viability. However, little work has devoted understanding their effects on the physiology of envelope, one main targets this clinical regimen. Herein, we use metabolic labeling methods visualize TB envelope dynamics mycobacterial species. We developed a new fluorophore–trehalose conjugate trehalose monomycolates mycomembrane using super‐resolution microscopy....
Abstract: Tuberculosis (TB) is the leading cause of death from an infectious bacterial disease. Poor diagnostic tools to detect active disease plague TB control programs and affect patient care. Accurate detection live Mycobacterium tuberculosis (Mtb), causative agent TB, will improve diagnosis treatment. We report that mycobacteria can be specifically detected with a fluorogenic trehalose analog. designed 4- N , -dimethylamino-1,8- naphthalimide-trehalose (DMN-Tre) conjugate undergoes...