A5007114172- Analytical Chemistry and Chromatography
- Mass Spectrometry Techniques and Applications
- Protein purification and stability
- Chromatography in Natural Products
- Microfluidic and Capillary Electrophoresis Applications
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Metabolomics and Mass Spectrometry Studies
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Biosimilars and Bioanalytical Methods
- Viral Infectious Diseases and Gene Expression in Insects
- Crystallization and Solubility Studies
- Advanced Proteomics Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Catalysis and Immobilization
- Origins and Evolution of Life
- Free Radicals and Antioxidants
- Analytical chemistry methods development
- Enzyme Structure and Function
- Molecular Sensors and Ion Detection
- Supramolecular Self-Assembly in Materials
- Antimicrobial Peptides and Activities
Merck & Co., Inc., Rahway, NJ, USA (United States)
2016-2025
Merck Institute for Science Education
2016-2019
Materials Resources (United States)
2019
Merck (Japan)
2019
Novartis (Switzerland)
2013
Novartis (United States)
2012
Institut de Biologie et de Chimie des Protéines
1999-2011
Tris Pharma (United States)
2008
Université Claude Bernard Lyon 1
1999
Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order a few seconds achievable. Nevertheless, routine determinations to support stereochemical investigations pharmaceutical research and development, synthetic chemistry bioanalysis are still typically performed 5-20 min timescale, with many practitioners believing that sub-minute not representative molecules encountered day research. In this study we develop ultrafast...
Chromatographic separation and analysis of complex mixtures closely related species is one the most challenging tasks in modern pharmaceutical analysis. In recent years, two-dimensional liquid chromatography (2D-LC) has become a valuable tool for improving peak capacity selectivity. However, relatively slow speed chiral separations limited use stationary phases (CSPs) as second dimension 2D-LC, especially comprehensive mode. Realizing that revolution field ultrafast enantioselective could...
Chromatographic separation, analysis and characterization of complex highly polar analyte mixtures can often be very challenging using conventional separation approaches. Analysis purification hydrophilic compounds have been dominated by liquid chromatography (LC) ion-exchange (IC), with sub/supercritical fluid (SFC) moving toward these new applications beyond traditional chiral separations. However, the low polarity supercritical carbon dioxide (CO2) has limited use SFC for in bioanalytical...
Manufacturing process development of new drug substances in the pharmaceutical industry combines numerous chemical challenges beyond efficient synthesis complex molecules. Optimization a synthetic route involves screening multiple reaction variables with desired outcome that not only depends on an increased product yield but is also highly influenced by removal efficacy residual chemicals and byproducts during subsequent route. Consequently, organic chemists must survey wide array to develop...
Enantioselective chromatography has been the preferred technique for determination of enantiomeric excess across academia and industry. Although sequential multicolumn enantioselective supercritical fluid screenings are widespread, access to automated ultra-high-performance liquid (UHPLC) platforms using state-of-the-art small particle size chiral stationary phases (CSPs) is an underdeveloped area. Herein, we introduce a UHPLC screening workflow capable combining 14 columns (packed with...
The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability methodologies site-selective modification biomolecules remains a long-standing challenge, given the inherent complexity and presence repeating residues that bear functional groups with similar reactivity profiles. We describe bioconjugation strategy native peptides relying on high site selectivity conveyed by enzymes. engineered penicillin G acylases to distinguish among free...
In recent years, the use of halogen-containing molecules has proliferated in pharmaceutical industry, where incorporation halogens, especially fluorine, become vitally important for blocking metabolism and enhancing biological activity pharmaceuticals. The chromatographic separation pharmaceuticals from associated isomers or dehalogenation impurities can sometimes be quite difficult. an attempt to identify best current tools available addressing this problem, a survey suitability four method...
Modern process research and development can often be hampered by the tedious method required to chromatographically resolve mixtures of chemical species with very similar physical properties. Herein, we describe a simple approach for implementation an efficient ultra-high performance liquid chromatography (UHPLC) assay that is extensively applied separation analysis multicomponent reaction closely related pharmaceutical intermediates impurities. Methods are optimized using multi-column...
At the forefront of chemistry and biology research, development timelines are fast-paced large quantities pure targets rarely available. Herein, we introduce a new framework, which is built upon an automated, online trapping-enrichment multi-dimensional liquid chromatography platform (TE-Dt-mDLC) that enables: 1) highly efficient separation complex mixtures in first dimension (1 D-UV); 2) automated peak buffer removal achieved through sequence H2 O D2 washes using independent pump setup; 3)...
Biotherapeutics are a prominent class of molecules used to treat wide range diseases, including cancer, infections, inflammatory and immune disorders. Advances in recombinant protein engineering have led the development therapeutic antibodies with multi-specific attributes increasingly complex structural functional formats. The discovery workflow involves high-throughput screening critical quality using liquid chromatography (LC) optimize cell line facilitate drug candidate selection....
Glycans of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein are speculated to play functional roles in infection processes as they extensively cover surface and highly conserved across variants. The has been principal target for vaccine therapeutic development while exact effects its glycosylation remain elusive. Analytical reports have described glycan heterogeneity protein. Subsequent molecular simulation studies provided a knowledge basis functions. However,...
Recent developments in the fields of organic synthesis, process research, and biopharmaceuticals are leading to increasingly complex mixtures closely related species that often prove challenging for analysis, separation, characterization. Herein, computer-assisted modeling using LC Simulator (ACD/Labs) software is introduced as an initial analytical framework isolation purification workflows, enabling rapid increase scale-up productivity (kkD: kilograms purified analyte per kilogram...
Temperature dependent inversion of enantioselectivity in asymmetric catalysis is an interesting and somewhat unusual phenomenon. We have observed temperature the autocatalysis reaction when triggered by a wide scope enantioenriched alcohols amines. The addition diisopropylzinc to pyrimidine-5-carbaldehyde presence enantiopure or amines affords pyrimidyl alkanol product at 0 °C with high ee. However, lowering -44 opposite enantioselectivity.
Inhibitor cystine knot peptides, derived from venom, have evolved to block ion channel function but are often toxic when dosed at pharmacologically relevant levels in vivo. The article describes the design of analogues ProTx-II that safely display systemic vivo blocking Nav1.7, resulting a latency response thermal stimuli rodents. new designs achieve better profile by improving selectivity and limiting ability peptides cause mast cell degranulation. rationale, structural modeling, vitro...
Abstract The separation of basic compounds can be challenging and the use inorganic mobile phase additives have been successfully used in chromatographic methods development. About fifteen years ago role these as ion-interaction agents for selectively adjusting retention ionic analytes was discovered theory chaotropicity applied to reversed chromatography. In last ten studies influence counterions on ionizable interaction with stationary various hydro-organic eluents has expanded our...
The goal of this study was to investigate the effect pressure modulation on retention, selectivity, and peak efficiency proteins small basic neutral molecules using reversed-phase liquid chromatography. A backpressure restrictor used in experiments variation at a constant flow rate. Experiments were conducted isocratic mode temperature mobile phase additives namely sodium perchlorate potassium hexafluorophosphate.