A5005950810- Protein purification and stability
- Energetic Materials and Combustion
- Mass Spectrometry Techniques and Applications
- Electromagnetic Launch and Propulsion Technology
- Monoclonal and Polyclonal Antibodies Research
- Advanced Proteomics Techniques and Applications
- Prion Diseases and Protein Misfolding
- Nuclear Physics and Applications
- Enzyme Structure and Function
- Viral Infectious Diseases and Gene Expression in Insects
- Plasma Diagnostics and Applications
- Radioactive contamination and transfer
- Advanced biosensing and bioanalysis techniques
- Electrochemical sensors and biosensors
- Glycosylation and Glycoproteins Research
- Coal and Its By-products
- Adenosine and Purinergic Signaling
- Alcoholism and Thiamine Deficiency
- Trace Elements in Health
- Research on Leishmaniasis Studies
- Analytical Chemistry and Chromatography
- Calcium signaling and nucleotide metabolism
- Clinical Laboratory Practices and Quality Control
- Molecular Junctions and Nanostructures
- Gyrotron and Vacuum Electronics Research
Adimab (United States)
2017-2025
AstraZeneca (United States)
2020
Altimmune (United States)
2019
Shanghai Institute of Measurement and Testing Technology
2015
Southern Medical University
2010
Eli Lilly (United States)
2009-2010
Zhujiang Hospital
2010
Case Western Reserve University
2007-2009
SUNY Polytechnic Institute
1991-2005
Nanjing University
2002
Propagation of transmissible spongiform encephalopathies is associated with the conversion normal prion protein, PrP C , into a misfolded, oligomeric form, Sc . Although high-resolution structure well characterized, structural properties remain elusive. Here we used MS analysis H/D backbone amide exchange to examine amyloid fibrils formed by recombinant human corresponding residues 90–231 (PrP90–231), misfolded form recently reported be infectious in transgenic mice overexpressing Analysis...
Contemporary in vivo and vitro discovery platform technologies greatly increase the odds of identifying high-affinity monoclonal antibodies (mAbs) towards essentially any desired biologically relevant epitope. Lagging throughput is ability to select for highly developable mAbs with drug-like properties early process. Upstream consideration developability metrics should reduce frequency failures later development stages. As field moves incorporating biophysical screening assays parallel...
CD73 (ecto-5'-nucleotidase) has recently been established as a promising immuno-oncology target. Given its role in activating purinergic signaling pathways to elicit immune suppression, antagonizing (i.e., releasing the brake) offers complimentary pathway inducing anti-tumor responses. Here, we describe mechanistic activity of new clinical therapeutic, MEDI9447, human monoclonal antibody that non-competitively inhibits activity. Epitope mapping, structural, and studies revealed MEDI9447...
Susceptibility of methionine to oxidation is an important concern for chemical stability during the development a monoclonal antibody (mAb) therapeutic. To minimize downstream risks, leading candidates are usually screened under forced conditions identify oxidation-labile molecules. Here we report results on large set in-house expressed and purified mAbs with variable region sequences corresponding 121 clinical stage mAbs. These mAb samples were treated 0.1% H2O2 24 hours before enzymatic...
The detailed structures of prion disease-associated, partially protease-resistant forms protein (e.g. PrP(Sc)) are largely unknown. PrP(Sc) appears to propagate itself by autocatalyzing the conformational conversion and oligomerization normal (PrP(C)). One manifestation templating activity is its ability, in misfolding cyclic amplification reactions, seed recombinant (rPrP) into aggregates that more closely resemble than spontaneously nucleated rPrP amyloids terms proteolytic fragmentation...
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...
The correct pairing of cognate heavy and light chains is critical to the efficient manufacturing IgG-like bispecific antibodies (bsAbs) from a single host cell. We present general solution for elimination chain (HC):light (LC) mispairs in bsAbs with κ LCs via use two orthogonal constant domain (CH1:Cκ) interfaces comprising computationally designed amino acid substitutions. Substitutions were by Rosetta introduce novel hydrogen bond (H-bond) networks at CH1:Cκ interface, followed energy...
Abstract Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important mechanism of action for many therapeutic antibodies. A immunoglobulin (Ig) G 1 monoclonal antibody lost more than half its ADCC activity after heat stress at 40 °C 4 months. Size-exclusion and ion-exchange chromatography were used to fractionate various size charge variants from the stressed IgG . Physicochemical characterization these fractions revealed that a rarely seen crystallizable fragment (Fc) modification,...
An electrochemical DNA sensor based on the recognition of single-stranded yeast (ssDNA) immobilized gold electrode to its complementary ssDNA (cDNA) is presented for hybridization detection. The was covalently bound a self-assembled 3-mercaptopropionic acid monolayer by using water soluble N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) as linker. prevented nonspecific adsorption long chain surface. could selectively hybridize with cDNA in solution form double-stranded...
Poly(ethylene glycol) (PEG)ylation of peptides and proteins creates significant challenges for detailed structural characterization, such as PEG heterogeneity, site addition number attached PEGylated moieties. Recently, we published a novel LC/MS methodology with post-column amines to obtain accurate masses proteins. The can be used assign the structures PEGs [15], but PEGylation remains unclear in situations where multiple potential attachments are involved. Here, present combining...
Racemization of amino acids is a common chemical degradation pathway observed in biopharmaceuticals and particularly prevalent synthetic peptides. The identification racemized acid residue(s) by mass spectrometry challenging due to isobaric between the isomeric forms. In this paper, we present novel methodology combining stable deuterium labeling with collisionally induced dissociation-tandem (CID-MS/MS) elucidate residues immunoglobulin samples. Immunoglobulin G subclasses IgG1, IgG2, IgG4...
A computer model, previously validated, was used to study the performance of an experimental three-phase launcher energized by a capacitor bank and designed impart 137 gram projectile muzzle velocity 500 m/s: (1) build-up traveling wave examined; (2) connection drive coils changed; (3) resistances circuits were calculated measured; (4) effect conductivity cylindrical tube (sleeve) constituting assessed. Experimentally, doubling achieved, from earlier-obtained 250 m/s, its present 476 m/s....
The work on the linear induction launcher (LIL) started with an analytical study that was followed by computer simulations and then tested laboratory models. Two mathematical representations have been developed to describe launcher. first, based field approach sinusoidal excitation, has validated static tests a small-scale prototype fed at constant current variable frequency. second, transient representation using simulation, allows consideration of energization means capacitor bank power...
In the linear induction launcher (LIL), barrel is divided into sections, and each one energized in polyphase fashion by discharging a capacitor bank through drive coils. The voltages frequency of currents coils progressively increase along barrel, from breech to muzzle. this paper, transition between sections two-section launcher, designed for muzzle velocity 500 m/s, investigated with aid computer simulation, previously validated. It shown that relatively insensitive location projectile at...
This paper describes the design, construction, and testing of a 500 m/s linear induction launcher (LIL). name was derived from its principle operation which is similar to that classical motor. Various theoretical models computer simulation codes were developed, have been validated experimentally in laboratory prototypes. The 'results published previously. LIL system built provide scaling-up guidelines for engineering higher- energy system. At print time, muzzle velocities up 250 achieved 134...
Asparagine (Asn) deamidation is a common posttranslational modification in which Asn converted to aspartic acid or isoaspartic acid. By introducing negative charge, could potentially impact the binding interface and biological activities of protein therapeutics. We identified variant moxetumomab pasudotox, an immunotoxin Fv fusion drug derived from 38-kDa truncated Pseudomonas exotoxin A (PE38) for treatment hairy-cell leukemia. Although site, Asn-358, was outside interface, had significant...
The performance of a two-section three-phase capacitor-driven LIL is analyzed by means computer simulation code which based on the transient behavior lumped circuit model representing gun. Initially, to design this launcher, select dimensions, and do preliminary calculations performance, simple steady-state sinusoidal operation was assumed. However, when dimensions were entered into code, code-predicted differed from results obtained using simplistic model. reasons for most departures can be...
The spreadsheet file reported herein provides centroid data, descriptive of deuterium uptake, for the FabFragment NISTmAb (PDB: 5K8A) reference material, as measured by bottom-up hydrogen-deuterium exchange mass spectrometry (HDX-MS) method. protein sample was incubated in deuterium-rich solutions under uniform pH and salt concentrations between 3.6 oC 25.4 seven intervals ranging over (0 to 14,400) s plus a ∞pseudo control. content peptic peptide fragments were spectrometry. These data...