A5089082798- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Analytical Chemistry and Chromatography
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Protein purification and stability
- Enzyme Structure and Function
- Ion-surface interactions and analysis
- Advanced Proteomics Techniques and Applications
- Biochemical and Structural Characterization
- Receptor Mechanisms and Signaling
- Viral Infectious Diseases and Gene Expression in Insects
University of Manchester
2016-2022
Covance (United Kingdom)
2021
Protéomique, Réponse Inflammatoire et Spectrométrie de Masse
2019
To quantify the measurable structural heterogeneity of a biopharmaceutical product and effect glycosylation on this we systematically evaluate three lots Herceptin®, two mAb standards an intact 5 Fc-hinge fragment.
The effect of temperature on the stability proteins is well explored above 298 K, but harder to track experimentally below 273 K. Variable-temperature ion mobility mass spectrometry (VT IM-MS) allows us measure structure molecules at sub-ambient temperatures. Here we monitor conformational changes that occur two isotypes monoclonal antibodies (mAbs) cooling by measuring their collision cross sections (CCS) discrete drift gas temperatures from 295 160 CCS 250 K larger than predicted...
In the development of therapeutic antibodies and biosimilars, an appropriate biopharmaceutical CMC control strategy that connects critical quality attributes with mechanism action should enable product assessment at early stage in order to mitigate risk. Here we demonstrate a new analytical workflow using trastuzumab which comprises "middle-up" analysis combination IdeS endoglycosidases EndoS EndoS2 comprehensively map glycan content. Enzymatic cleavage between two N-acetyl glucosamine...
The gas phase is an idealized laboratory for the study of protein structure, from which it possible to examine stable and transient forms mass-selected ions in absence bulk solvent. With ion mobility–mass spectrometry (IM-MS) apparatus built operate at both cryogenic elevated temperatures, we have examined conformational transitions that occur monomeric proteins: ubiquitin, lysozyme, α-synuclein as a function temperature source activation. We rationalize experimental observations with...
Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity biopharmaceuticals, with a significant number techniques methods available to perform these measurements. The comparison the analytical performance HOS standardization results is, however, not trivial task, due lack reference protocols measurement procedures. Here, we developed protocol structurally alter compare samples somatropin, recombinant...
The gas phase is an idealized laboratory for the study of protein structure, from which it possible to examine stable and transient forms mass selected ions in absence bulk solvent. With ion mobility-mass spectrometry (IM-MS) apparatus built operate at both cryogenic elevated temperatures, we have examined conformational transitions monomeric proteins: ubiquitin, lysozyme alpha-synuclein as a function temperature source activation. We rationalize experimental observations with dependent...
Abstract The effect of temperature on the stability proteins is well explored above 298 K, but harder to track experimentally below 273 K. Variable‐temperature ion mobility mass spectrometry (VT IM‐MS) allows us measure structure molecules at sub‐ambient temperatures. Here we monitor conformational changes that occur two isotypes monoclonal antibodies (mAbs) cooling by measuring their collision cross sections (CCS) discrete drift gas temperatures from 295 160 CCS 250 K larger than predicted...
<p>As experimentalists, we normally rely on assessing observables. However sometimes, the most fascinating phenomena are not noticeable directly. An example of such is our data and corresponding interpretation presented in this manuscript. We have designed constructed a ion mobility mass spectrometer (acs.analchem.6b01812) capable taking measurements over temperature range from 150-500K. chose to benchmark new instrument, using small proteins Ubiquitin Lysozyme extensively studied as...
As experimentalists, we normally rely on assessing observables. However sometimes, the most fascinating phenomena are not noticeable directly. An example of such is our data and corresponding interpretation presented in this manuscript. We have designed constructed a ion mobility mass spectrometer (acs.analchem.6b01812) capable taking measurements over temperature range from 150-500K. chose to benchmark new instrument, using small proteins Ubiquitin Lysozyme extensively studied as “model...
<p>To consider the measurable variations in biopharmaceuticals we use mass spectrometry and systematically evaluate three lots of Herceptin®, two mAb standards an intact Fc-hinge fragment. Each is examined states; glycan intact, truncated (following endoS2 treatment) fully deglycosylated. Despite equivalence at protein level, each lot Herceptin® gives a distinctive signature different analyses. Ion mobility (IM-MS) shows that API, attached N-glycans reduce conformational spread by 10.5...
To consider the measurable variations in biopharmaceuticals we use mass spectrometry and systematically evaluate three lots of Herceptin®, two mAb standards an intact Fc-hinge fragment. Each is examined states; glycan intact, truncated (following endoS2 treatment) fully deglycosylated. Despite equivalence at protein level, each lot Herceptin® gives a distinctive signature different analyses. Ion mobility (IM-MS) shows that API, attached N-glycans reduce conformational spread by 10.5 – 25 %....
As experimentalists, we normally rely on assessing observables. However sometimes, the most fascinating phenomena are not noticeable directly. An example of such is our data and corresponding interpretation presented in this manuscript. We have designed constructed a ion mobility mass spectrometer (acs.analchem.6b01812) capable taking measurements over temperature range from 150-500K. chose to benchmark new instrument, using small proteins Ubiquitin Lysozyme extensively studied as “model...
The effect of temperature on the stability proteins is well explored for high temperatures, but harder to track below freezing point water. This challenge met with use variable ion mobility mass spectrometry (VT IM-MS), which allows structure isolated, solvent free molecules be measured at sub ambient temperatures in form their collision cross section (CCS). Here we monitor conformational changes that occur two isotypes monoclonal antibodies over a range from 295 165 K. For each observe...
The gas phase is an idealized laboratory for the study of protein structure, from which it possible to examine stable and transient forms mass selected ions in absence bulk solvent. With ion mobility-mass spectrometry (IM-MS) apparatus built operate at both cryogenic elevated temperatures, we have examined conformational transitions monomeric proteins: ubiquitin, lysozyme alpha-synuclein as a function temperature source activation. We rationalize experimental observations with dependent...