A5036482163- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Lipid Membrane Structure and Behavior
- Immunotherapy and Immune Responses
- Bone Metabolism and Diseases
- Lipoproteins and Cardiovascular Health
- Bone health and treatments
- Radiopharmaceutical Chemistry and Applications
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Force Microscopy Techniques and Applications
- Protein purification and stability
- Muscle metabolism and nutrition
- Infectious Encephalopathies and Encephalitis
- NF-κB Signaling Pathways
- Tissue Engineering and Regenerative Medicine
- Biochemical and Structural Characterization
- Vitamin D Research Studies
- Mechanical and Optical Resonators
- Cancer Immunotherapy and Biomarkers
- Molecular Junctions and Nanostructures
- Bacterial Genetics and Biotechnology
- Genomics and Chromatin Dynamics
- Immune Response and Inflammation
- Muscle Physiology and Disorders
Bristol-Myers Squibb (United States)
2011-2020
Bristol-Myers Squibb (Germany)
2014
Protein Express (United States)
2011
University of Pennsylvania
2005-2007
Children's Hospital of Philadelphia
2005
CSL (United States)
2003
GlaxoSmithKline (Netherlands)
1999
Pennsylvania State University
1999
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...
Duchenne muscular dystrophy (DMD) is a genetic muscle disorder that manifests during early childhood and ultimately fatal. Recently approved treatments targeting the cause of DMD are limited to specific subpopulations patients, highlighting need for therapies with wider applications. Pharmacologic inhibition myostatin, an endogenous inhibitor growth produced almost exclusively in skeletal muscle, has been shown increase mass several species, including humans. Taldefgrobep alfa anti-myostatin...
The receptor activator of NF-kappaB (RANK) belongs to the neuregulin/tumor necrosis factor (TNF) superfamily and is activated by RANK ligand (RANK-L), a homotrimeric, TNF-like cytokine. present on surface osteoclast cell precursors, where its interaction with RANK-L induces their terminal differentiation into osteoclasts, thus increasing bone breakdown. secreted, soluble osteoprotegerin (OPG) interrupts this activation binding directly RANK-L. Therefore, maturation (and homeostasis)...
Mounting evidence in models of both autoimmunity and chronic viral infection suggests that the outcome T cell activation is critically impacted by constellation co-stimulatory co-inhibitory receptors expressed on surface. Here, we identified a critical role for SLAM family member 2B4 (CD244) attenuating primary antigen-specific CD8+ responses presence immune modulation with selective CD28 blockade. Our results reveal specific up-regulation cells animals which signaling was blocked. However,...
Targeting the CD28-CD80/86 pathway with an anti-CD28 antagonist is a promising alternative to current therapies for autoimmunity. However, attempts at generating conventional mAbs lacking stimulatory activity has been challenging. In this study, we describe anti-human CD28 receptor domain Abs (dAbs) that are specific human CD28. These dAbs potent inhibitors of T cell activation, EC50 35 ± 14 ng/ml inhibition proliferation. The 53 11 in ex vivo occupancy assay corresponds vitro functional...
The structure of death receptor 4 (DR4) in complex with TNF-related apoptosis-inducing ligand (TRAIL) has been determined at 3 Å resolution and compared those previously DR5–TRAIL complexes. Consistent the high sequence similarity between DR4 DR5, overall arrangement DR4–TRAIL does not differ substantially from that complex. However, subtle differences are apparent. In addition, solution interaction studies were carried out show thermodynamics binding or DR5 TRAIL.
Apolipoprotein E (apoE) is a key regulator of cholesterol homeostasis. Human apoE has three common isoforms, each with different risk implications for cardiovascular and neurodegenerative disease. Neither the structure lipoprotein particles nor structural consequences isoform differences are known. In this investigation, synthetic were prepared by complexing phospholipids full-length or truncated N-terminal C-terminal domains apoE. These examined calorimetry, electron microscopy, circular...
It is well accepted that high levels of density lipoproteins (HDL) reduce the risk atherosclerosis in humans. Apolipoprotein A-I (apoA-I) and apoA-II are first second most common protein constituents HDL. Unlike apoA-I, detailed structural models for HDL not available. Here, we present a model reconstituted (rHDL) based on two established experimental approaches: chemical cross-linking/mass spectrometry (MS) internal reflection infrared spectroscopy. Homogeneous rHDL were reacted with...
BMS-931699 (lulizumab pegol), a domain antibody (dAb) conjugated with 40-kDa branched polyethylene glycol, is human anti-CD28 receptor antagonist under development for the treatment of inflammatory and autoimmune diseases. In present work, minimal anticipated biologic effect level (MABEL) was determined by integrating all available preclinical data. The relevance in vitro mixed lymphocyte reaction (MLR) assay to whole blood CD28 occupancy (RO) assessment, as well relationship between RO...
Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte expressed on cells of granulocytic lineage. Recombinant forms are used clinically treat neutropenias. As part an effort develop mimics with potential for oral bioavailability, we previously identified nonpeptidyl small molecule (SB-247464) that selectively activates murine signal transduction pathways and promotes formation <i>in vivo</i>. To elucidate mechanism action...
A kinetic analysis of dimer dissociation, TATA DNA binding, and thermal inactivation the yeast Saccharomyces cerevisiae human binding proteins (TBP) was conducted. We find that TBP dimers, like are slow to dissociate in vitro (t1/2 ∼20 min). Mild mutations crystallographic interface accelerate rate whereas severe prevent dimerization. In presence excess DNA, which measures entire active population, dissociation represents rate-limiting step binding. These findings provide a biochemical...
Advances in vitro display and protein engineering yield therapeutics with affinities the picomolar range. The Gyrolab® microfluidics platform uses kinetic exclusion assay principle to measure subnanomolar solution affinities. This work describes application of Gyrolab affinity module new multi-curve analysis feature determine PD-L1 Adnectin™ positron emission tomography radioligand, which was measured as 20 pM for human PD-L1. We also report key parameters that affect signal-to-background...
Mounting evidence in models of both autoimmunity and chronic viral infection suggests that the outcome T cell activation is critically impacted by constellation costimulatory coinhibitory receptors expressed on cells' surface. Here, we identified a critical role for SLAM family member 2B4 (CD244) attenuating primary donor-reactive CD8+ responses presence immune modulation with selective CD28 blockade. Our results reveal specific upregulation cells animals which signaling was blocked....
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