[NMR paper] Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
Protein-based drugs are becoming increasingly important, but there are challenges associated with their formulation (for example, formulating stable inhalable aerosols while maintaining the proper long-term stability of the protein). Determining the morphology of multicomponent, protein-based drug formulations is particularly challenging. Here, we use dynamic nuclear polarization (DNP) solid-state NMR spectroscopy to determine the hierarchy of components within spray-dried particles...
nmrlearner
Journal club
0
10-03-2023 02:16 AM
[NMR paper] Ranking mAb-excipient interactions in biologics formulations by NMR spectroscopy and computational approaches
Ranking mAb-excipient interactions in biologics formulations by NMR spectroscopy and computational approaches
Excipients are added to biopharmaceutical formulations to enhance protein stability and enable the development of robust formulations with acceptable physicochemical properties, but the mechanism by which they confer stability is not fully understood. Here, we aimed to elucidate the mechanism through direct experimental evidence of the binding affinity of an excipient to a monoclonal antibody (mAb), using saturation transfer difference (STD) nuclear magnetic resonance (NMR)...
nmrlearner
Journal club
0
05-23-2023 05:05 PM
[NMR paper] Investigating protein-excipient interactions of a multivalent VHH therapeutic protein using NMR spectroscopy
Investigating protein-excipient interactions of a multivalent VHH therapeutic protein using NMR spectroscopy
Fab Fragment antigen-binding; Fc Fragment crystallizable; HMW High molecular weight; ?HMW Difference between HMW species at stress temperature and 5°C controls; IgG Immunoglobulin G; mAbs Monoclonal antibodies; MV-V(HH) Multivalent V(HH) molecule with the format aC-L(1)-aC-L(1)-aD; NMR Nuclear magnetic resonance; scFv Single-chain fragment variable; SEC Size-exclusion chromatography; V(HH) Variable domain of Heavy chain of Heavy chain-only antibody.
More...
nmrlearner
Journal club
0
09-28-2022 06:29 AM
[NMR paper] Comprehensive Assessment of Protein and Excipient Stability in Biopharmaceutical Formulations Using (1)H NMR Spectroscopy
Comprehensive Assessment of Protein and Excipient Stability in Biopharmaceutical Formulations Using (1)H NMR Spectroscopy
Biopharmaceutical proteins are important drug therapies in the treatment of a range of diseases. Proteins, such as antibodies (Abs) and peptides, are prone to chemical and physical degradation, particularly at the high concentrations currently sought for subcutaneous injections, and so formulation conditions, including buffers and excipients, must be optimized to minimize such instabilities. Therefore, both the protein and small molecule content of biopharmaceutical...
nmrlearner
Journal club
0
03-04-2021 12:41 PM
Pairwise binding competition experiments for sorting hub-protein/effector interaction hierarchy and simultaneous equilibria
Pairwise binding competition experiments for sorting hub-protein/effector interaction hierarchy and simultaneous equilibria
Abstract
NMR experiments on proteins in simultaneous equilibria with multiple binding partners can provide a tool to understand complex biological interaction networks. Competition among proteins for binding to signaling hubs is often at the basis of the information transmission across signaling networks in every organism. Changes in affinity towards one or more partners, as well as changes of the relative concentration of the...
nmrlearner
Journal club
0
07-12-2014 06:07 PM
[NMR paper] A solid-state NMR study of molecular mobility and phase separation in co-spray-dried
A solid-state NMR study of molecular mobility and phase separation in co-spray-dried protein-sugar particles.
Related Articles A solid-state NMR study of molecular mobility and phase separation in co-spray-dried protein-sugar particles.
Eur J Pharm Sci. 2005 May;25(1):105-12
Authors: Suihko EJ, Forbes RT, Apperley DC
Molecular mobility and physical form of co-spray-dried sugar-lysozyme formulations were evaluated. Co-spray-dried trehalose:lysozyme and sucrose:lysozyme formulations in 1:9, 1:1 and 9:1 ratios (w:w) were stored at 0% RH and 75%...
nmrlearner
Journal club
0
11-25-2010 08:21 PM
[NMR paper] NMR elucidation of early folding hierarchy in HIV-1 protease.
NMR elucidation of early folding hierarchy in HIV-1 protease.
Related Articles NMR elucidation of early folding hierarchy in HIV-1 protease.
J Biol Chem. 2003 May 30;278(22):19980-5
Authors: Bhavesh NS, Sinha R, Mohan PM, Hosur RV
Folding studies on proteases by the conventional hydrogen exchange experiments are severely hampered because of interference from the autolytic reaction in the interpretation of the exchange data. We report here NMR identification of the hierarchy of early conformational transitions (folding propensities) in HIV-1...