- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Proteoglycans and glycosaminoglycans research
- Protein Tyrosine Phosphatases
- Click Chemistry and Applications
- Genetics, Bioinformatics, and Biomedical Research
- Protein Kinase Regulation and GTPase Signaling
- Viral Infectious Diseases and Gene Expression in Insects
- Receptor Mechanisms and Signaling
- Influenza Virus Research Studies
- Virus-based gene therapy research
- Biotin and Related Studies
- Bioinformatics and Genomic Networks
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Multiple Myeloma Research and Treatments
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Cholinesterase and Neurodegenerative Diseases
- RNA modifications and cancer
- Adipokines, Inflammation, and Metabolic Diseases
- 14-3-3 protein interactions
Amgen (United States)
2023-2024
Janssen (United States)
2020-2022
Springhouse
2018
United States Military Academy
2016
Johnson & Johnson (United States)
2012
Bristol-Myers Squibb (United States)
2010-2012
Princeton University
2011
LifeSensors (United States)
2005
National Institute of Environmental Health Sciences
2004
National Institutes of Health
2004
Despite the availability of numerous gene fusion systems, recombinant protein expression in Escherichia coli remains difficult. Establishing best partner for difficult-to-express proteins empirical. To determine which tags are suited proteins, a comparative analysis newly described SUMO system with variety commonly used systems was completed. For this study, three model enhanced green fluorescent (eGFP), matrix metalloprotease-13 (MMP13), and myostatin (growth differentiating factor-8,...
Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function viral replication as integral component of ribonucleoprotein complex, associating with RNA and polymerase within core. The multifunctional nature NP makes it attractive target for antiviral intervention, inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered structurally similar series influenza show that they interfere NP-dependent processes...
Inhibition of signal transduction downstream the IL-23 receptor represents an intriguing approach to treatment autoimmunity. Using a chemogenomics marrying kinome-wide inhibitory profiles compound library with cellular activity against IL-23-stimulated transcriptional response in T lymphocytes, class inhibitors was identified that bind and stabilize pseudokinase domain Janus kinase tyrosine 2 (Tyk2), resulting blockade receptor-mediated activation adjacent catalytic domain. These Tyk2...
The near impermeability of the blood-brain barrier (BBB) and unique neuroimmune environment CNS prevents effective use antibodies in neurological diseases. Delivery biotherapeutics to brain can be enabled through receptor-mediated transcytosis via proteins such as transferrin receptor, although limitations ability Fc-mediated effector function clear pathogenic targets introduce safety liabilities. Hence, novel delivery approaches with alternative clearance mechanisms are warranted.Binders...
Heparan sulfate (HS) plays essential roles in assisting herpes simplex virus infection and other biological processes. The biosynthesis of HS includes numerous specialized sulfotransferases that generate a variety sulfated saccharide sequences, conferring the selectivity functions HS. We report structural study human 3-<i>O</i>-sulfotransferase isoform 3 (3-OST-3), key sulfotransferase transfers sulfuryl group to specific glucosamine generating an entry receptor for 1. have obtained crystal...
Heparan sulfate interacts with antithrombin, a protease inhibitor, to regulate blood coagulation. 3-O-sulfotransferase isoform 1 performs the crucial last step modification in biosynthesis of anticoagulant heparan sulfate. This enzyme transfers sulfuryl group (SO3) from 3′-phosphoadenosine 5′-phosphosulfate 3-OH position glucosamine residue form 3-O-sulfo glucosamine, structural motif critical for binding antithrombin. In this study, we report crystal structure at 2.5-Å resolution binary...
Generative biology combines artificial intelligence (AI), advanced life sciences technologies, and automation to revolutionize the process of designing novel biomolecules with prescribed properties, giving drug discoverers ability escape limitations during design next-generation protein therapeutics. Significant hurdles remain, namely: (i) inherently complex nature discovery, (ii) bewildering number promising computational experimental techniques that have emerged in past several years,...
The long circulating half-life and inherently bivalent architecture of IgGs provide an ideal vehicle for presenting otherwise short-lived G-protein-coupled receptor agonists in a format that enables avidity-driven enhancement potency. Here, we describe the site-specific conjugation dual agonist peptide (an oxyntomodulin variant engineered potency vivo stability) to complementarity-determining regions (CDRs) immunologically silent IgG4. A cysteine-containing heavy chain CDR3 was identified...
The 3-O-sulfation of glucosamine by heparan sulfate 3-O-sulfotransferase-1 (3-OST-1) is a key modification step during the biosynthesis anticoagulant (HS). In this paper, we present evidence conformational change that occurs in 3-OST-1 upon binding to sulfate. intrinsic fluorescence was increased presence HS, suggesting change. This apparent further investigated using differential chemical measure solvent accessibility lysine residues. treated with acetic anhydride either or absence HS both...
Protein-protein interactions identified through high-throughput proteomics efforts continue to advance our understanding of the protein interactome. In addition highly specific protein-protein interactions, it is becoming increasingly more common for yeast two-hybrid, pull-down assays, and other techniques identify multiple ligands that bind same target protein. A resulting challenge accurately characterize assembly these multiprotein complexes competition among a given target. The...