A5044887566- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Viral Infectious Diseases and Gene Expression in Insects
- Microfluidic and Capillary Electrophoresis Applications
- Microfluidic and Bio-sensing Technologies
- Peptidase Inhibition and Analysis
- Protein Structure and Dynamics
- Lysosomal Storage Disorders Research
- Lipid Membrane Structure and Behavior
- Trace Elements in Health
- Advanced Proteomics Techniques and Applications
- Parathyroid Disorders and Treatments
- Neuroendocrine Tumor Research Advances
- HER2/EGFR in Cancer Research
- Enzyme Structure and Function
- Spectroscopy and Quantum Chemical Studies
- Biological Research and Disease Studies
- Mass Spectrometry Techniques and Applications
- thermodynamics and calorimetric analyses
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Thyroid Disorders and Treatments
- Ion channel regulation and function
- Biochemical and Molecular Research
- DNA and Nucleic Acid Chemistry
Sanofi (United States)
2015-2024
Center for Global Development
2021-2023
Boston University
2007-2012
Amyloidosis Foundation
2012
University of New Hampshire
2000-2004
Colloidal interactions in dilute solution singularly enable selection of well-behaved antibodies during drug discovery.
There is significant interest in formulating antibody therapeutics as concentrated liquid solutions, but early identification of developable antibodies with optimal manufacturability, stability, and delivery attributes remains challenging. Traditional methods identifying mAbs low self-association common formulations require relatively protein solutions (>1 mg/mL), this single challenge has frustrated early-stage large-scale candidates drug-like colloidal properties. Here, we describe...
Transthyretin (TTR) is normally a stable plasma protein. However, in cases of familial TTR-related amyloidosis and senile systemic (SSA), TTR deposited as amyloid fibrils, leading to organ dysfunction possibly death. The mechanism by which undergoes the transition from stable, soluble precursor insoluble fibril factors that promote this process are largely undetermined. Most models involve dissociation native tetramer initial step. It accepted gene mutations associated with lead expression...
Recombinant human α-galactosidase A (rhαGal) is a homodimeric glycoprotein deficient in Fabry disease, lysosomal storage disorder. In this study, each cysteine residue rhαGal was replaced with serine to understand the role plays enzyme structure, function, and stability. Conditioned media from transfected HEK293 cells were assayed for expression enzymatic activity. Activity only detected wild type control mutants substituting free residues (C90S, C174S, C90S/C174S). Cysteine-to-serine...
Wild-type transthyretin (TTR), normally a soluble plasma-circulating protein, can be amyloidogenic, i.e., form tissue-deposited fibrillar material in the extracellular matrix of various organs throughout body. Senile systemic amyloidosis (SSA) is one such pathology and features TTR-containing amyloid deposits that are found primarily heart. The cause for this transition from to insoluble protein SSA yet determined as specific structural might favor TTR fibrillogenesis have not been...
Thyrogen (thyrotropin alfa for injection), recombinant human TSH (rhTSH), has been successfully used to enhance diagnostic radioiodine scanning and thyroglobulin testing in the follow-up of patients with thyroid cancer as an adjunctive treatment remnant ablation. However, short half-life rhTSH circulation requires a multidose regimen. We developed novel sialic acid-mediated galactose-mediated conjugation chemistries targeting polyethylene glycol (PEG) three N-linked glycosylation sites on...
Recombinant human thyroid stimulating hormone (rhTSH or Thyrogen) has been approved for cancer diagnostics and treatment under a multidose regimen due to its short circulating half-life. To reduce dosing frequency, PEGylation strategies were explored increase the duration of action rhTSH. Lysine N-terminal resulted in heterogeneous product profiles with 40% lower reaction yields monoPEGylated products. Eleven cysteine mutants designed based on structure model TSH-TSH receptor (TSHR) complex...
Monoclonal antibodies (mAbs) are an important modality of protein therapeutics with broad applications for numerous diseases. However, colloidal instabilities occurring at high concentrations can limit the ability to develop stable, high-concentration liquid dosage forms that required patient-centric, device-mediated products. Therefore, it is advantageous identify colloidally stable mAbs early in discovery process ensure they selected development. Experimental screening stability be time-...
Short-chain C6-sphingomyelin is an artificial substrate that was used in acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann-Pick disease types A and B. Using previously published multiplex single conditions, normal levels (i.e. false negative results) were observed two sisters B who compound heterozygotes missense mutations, p.C92W p.P184L, the SMPD1 gene. Increasing sodium taurocholate detergent concentration buffer lowered these into range other clear...
Monoclonal antibodies (mAbs) are often formulated as high-protein-concentration solutions, which in some cases can exhibit physical stability issues such high viscosity and opalescence. To ensure that mAb-based drugs meet their manufacturing, stability, delivery requirements, it is advantageous to screen for select mAbs during discovery not prone behaviors. It has been recently shown both these macroscopic properties be predicted a certain extent from the diffusion interaction parameter...
Assessment of cold stability is essential for manufacture and commercialization biotherapeutics. Storage often estimated by measuring accelerated rates at elevated temperature using mathematical models (as the Arrhenius equation). Although, this strategy leads to an underestimation protein aggregation during storage. In work, we measured two antibodies in a broad range (from 60 °C -25 °C), isochoric cooling method prevent freezing formulations below 0 °C. Both evidenced increasing when...
Charges and their contribution to protein-protein interactions are essential for the key structural dynamic properties of monoclonal antibody (mAb) solutions. In fact, they influence apparent molecular weight, static structure factor, collective diffusion coefficient or relative viscosity concentration dependence. Further, charges play an important role in colloidal stability mAbs. There exist standard experimental tools characterise mAb net such as measurement electrophoretic mobility,...