A5072455989- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Protein purification and stability
- Glycosylation and Glycoproteins Research
- Analytical Chemistry and Chromatography
- Viral Infectious Diseases and Gene Expression in Insects
- Protein Structure and Dynamics
- Advanced Proteomics Techniques and Applications
- Catalytic Alkyne Reactions
- Catalytic Cross-Coupling Reactions
- Enzyme Structure and Function
- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Radiopharmaceutical Chemistry and Applications
- Photosynthetic Processes and Mechanisms
- Peptidase Inhibition and Analysis
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- Synthetic Organic Chemistry Methods
- T-cell and B-cell Immunology
- Complement system in diseases
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Algal biology and biofuel production
Bristol-Myers Squibb (United States)
2014-2022
Bristol-Myers Squibb (Germany)
2014-2021
National Institute of Standards and Technology
2013-2015
Bioanalytical Systems (United States)
2015
University of Maryland, Baltimore
2014
University of Maryland, College Park
2014
Institute for Bioscience and Biotechnology Research
2013-2014
Washington University in St. Louis
2010-2013
University of Toronto
2011-2013
Material Measurement Laboratory
2013
Bioconjugation technologies have revolutionized the practice of biology and medicine by allowing access to novel biomolecular scaffolds. New methods for residue-selective bioconjugation are highly sought expand toolbox a variety applications. Herein we report site-selective methionine protocol that uses photoexcited lumiflavin generate open-shell intermediates. This reduction-potential-gated strategy enables residues unavailable with traditional nucleophilicity-based conjugation methods. To...
Apolipoprotein E, a 34 kDa protein, plays key role in triglyceride and cholesterol metabolism. Of the three common isoforms (ApoE2, -3, -4), only ApoE4 is risk factor for Alzheimer's disease. All of wild-type ApoE self-associate to form oligomers, process that may have functional consequences. Although C-terminal domain, residues 216–299, believed mediate self-association, specific involved this are not known. Here we report use hydrogen/deuterium exchange (H/DX) coupled with enzymatic...
Epitope mapping is an important tool for the development of monoclonal antibodies, mAbs, as therapeutic drugs. Recently, a class mAb alternatives, adnectins, has been developed targeted biologics. They are derived from 10th type III domain human fibronectin ((10)Fn3). A common approach to map epitope binding these proteins their partners X-ray crystallography. Although crystal structure known Adnectin 1 epidermal growth factor receptor (EGFR), we seek determine complementary in solution and...
Photosystem II (PSII), a large multisubunit pigment–protein complex localized in the thylakoid membrane of cyanobacteria and chloroplasts, mediates light-driven evolution oxygen from water. Recently, high-resolution X-ray structure mature PSII has become available. Two polypeptides, D1 CP43, provide many ligands to an inorganic Mn 4 Ca center that is essential for water oxidation. Because its unusual redox chemistry, often undergoes degradation followed by stepwise assembly. Psb27, small...
A regio- and stereoselective rhodium-catalyzed synthesis of trisubstituted allylic alcohols is described. The utility these synthons demonstrated in a convenient indenes quinolines.
Epitope mapping the specific residues of an antibody/antigen interaction can be used to support mechanistic interpretation, antibody optimization, and epitope novelty assessment. Thus, there is a strong need for methods, particularly integrative ones. Here, we report identification energetic by determining interfacial hot-spot that dominates binding affinity anti-interleukin-23 (anti-IL-23) using complementary approaches hydrogen/deuterium exchange mass spectrometry (HDX-MS), fast...
Higher-order structure (HOS) is a crucial determinant for the biological functions and quality attributes of protein therapeutics. Mass spectrometry (MS)-based footprinting approaches play an important role in elucidating relationship between biophysical properties structure. Here, we describe use combined method including hydrogen-deuterium exchange (HDX), fast photochemical oxidation proteins (FPOP), site-specific carboxyl group to investigate HOS complexes. The work focuses on...
Hydrogen–deuterium exchange mass spectrometry (HDX-MS) is an established, powerful tool for investigating protein–ligand interactions, protein folding, and dynamics. However, HDX-MS still emergent quality control of biopharmaceuticals establishing dynamic similarity between a biosimilar innovator therapeutic. Because industry will conduct measurements over product lifetime in multiple locations, understanding reproducibility critical. To determine the continuous-labeling, bottom-up...
Programmed cell death-1 (PD-1), an antigen co-receptor on surfaces, is one of the conspicuous immune checkpoints. Nivolumab, a monoclonal antibody therapeutic approved by FDA, binds to PD-1 and efficiently blocks its pathways. In this study, integrated approach was developed map epitope/paratope PD-1/nivolumab. The includes hydrogen-deuterium exchange mass spectrometry (HDX-MS) followed electron-transfer dissociation (ETD), chemical cross-linking, molecular docking. HDX-ETD offers some...
We describe an integrated approach of using hydrogen–deuterium exchange mass spectrometry (HDX-MS), chemical cross-linking (XL-MS), and molecular docking to characterize the binding interface predict three-dimensional quaternary structure a protein–protein complex in solution. Interleukin 7 (IL-7) its α-receptor, IL-7Rα, serving as essential mediators immune system, are model system. HDX kinetics reports widespread protection on IL-7Rα but shows no differential evidence binding-induced or...
Connexin43 (Cx43) is a major cardiac gap junction channel protein required for normal electrical and contractile activity. Gap assembly, function, turnover are regulated by phosphorylation under both disease conditions. The carboxyl terminus (CT) of Cx43 contains numerous amino acid residues that phosphorylated kinases. However, our knowledge the specific kinases involved incomplete. objective this study was to identify in Cx43-CT targets multifunctional kinase, Ca(2+)/calmodulin kinase II...
TL1A, a tumor necrosis factor-like cytokine, is ligand for the death domain receptor DR3. upon binding to DR3, can stimulate lymphocytes and trigger secretion of proinflammatory cytokines. Therefore, blockade TL1A/DR3 interaction may be potential therapeutic strategy autoimmune inflammatory diseases. Recently, anti-TL1A monoclonal antibody 1 (mAb1) with strong potency in blocking was identified. Here, we report on use hydrogen/deuterium exchange mass spectrometry (HDX-MS) obtain...
CD47 is the only 5-transmembrane (5-TM) spanning receptor of immune system. Its extracellular domain (ECD) a cell surface marker self that binds SIRPα and inhibits macrophage phagocytosis, cancer immuno-therapy approaches in clinical trials are focused on blocking CD47/SIRPα interaction. We present crystal structure full length bound to function-blocking antibody B6H12. ECD tethered TM via six-residue peptide linker (114RVVSWF119) forms an extended loop (SWF loop), with fundamental role...
Human α1-acid glycoprotein (AGP), an acute-phase glycoprotein, exists predominantly in blood. With its ability to bind basic, lipophilic, and acidic drugs, AGP has served as a drug carrier. It been shown that the carbohydrate composition of changes response tissue injury, inflammation, or infection can have great impact on AGP's binding activities. The molecular-level details effects desialylation conformation AGP-ligand interactions, however, are unknown. Here we report use...
Accurate quantification of soluble glypican-3 in clinical samples using immunoassays is challenging, because the lack appropriate antibody reagents to provide a full spectrum measurement all potential fragments vivo. Glypican-3 SOMAmer (slow off-rate modified aptamer) novel reagent that binds, with high affinity, far distinct epitope glypican-3, when compared available generated in-house. This paper describes an integrated analytical approach rational selection key based on molecular...
In green-sulfur bacterial photosynthesis, excitation energy absorbed by a peripheral antenna structure known as the chlorosome is sequentially transferred through baseplate protein to Fenna-Matthews-Olson (FMO) and into reaction center, which embedded in cytoplasmic membrane. The molecular details of optimized photosystem architecture required for efficient transfer are only partially understood. We address here question how interacts with FMO applying hydrogen/deuterium exchange coupled...