Molecular Flexibility of Antibodies Preserved Even in the Dense Phase after Macroscopic Phase Separation
| العنوان: | Molecular Flexibility of Antibodies Preserved Even in the Dense Phase after Macroscopic Phase Separation |
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| المؤلفون: | Anita Girelli, Christian Lang, Orsolya Czakkel, Tilo Seydel, Christian Beck, Olga Matsarskaia, Frank Schreiber, Fajun Zhang, Famke Bäuerle, Felix Roosen-Runge, Ralph Maier, Baohu Wu |
| المساهمون: | Institut Laue-Langevin (ILL), ILL, ANR-16-CE92-0009,ImmunoglobulinCrowding,Propriétés statiques et dynamiques des protéines anticorps - l'influence de l'effet de 'crowding' et des charges(2016) |
| المصدر: | Molecular Pharmaceutics Molecular Pharmaceutics, American Chemical Society, 2021, ⟨10.1021/acs.molpharmaceut.1c00555⟩ Molecular pharmaceutics 18(11), 4162–4169 (2021). doi:10.1021/acs.molpharmaceut.1c00555 |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Flexibility (anatomy), Materials science, Chemistry, Pharmaceutical, Injections, Subcutaneous, Quantitative Biology::Tissues and Organs, Diffusion, Pharmaceutical Science, 02 engineering and technology, Neutron scattering, 010402 general chemistry, 01 natural sciences, Article, Polyethylene Glycols, Pharmaceutical Sciences, Viscosity, chemistry.chemical_compound, Molecular level, Molecular function, Phase (matter), Drug Discovery, medicine, ddc:610, antibody therapy, ComputingMilieux_MISCELLANEOUS, Neutrons, Spectrum Analysis, diffusion, Antibodies, Monoclonal, dynamics, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Farmaceutiska vetenskaper, 021001 nanoscience & nanotechnology, [PHYS.PHYS.PHYS-GEN-PH]Physics [physics]/Physics [physics]/General Physics [physics.gen-ph], 0104 chemical sciences, Solutions, molecular flexibility, medicine.anatomical_structure, chemistry, Chemical physics, Molecular Medicine, Pharmaceutical Vehicles, 0210 nano-technology, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], Ethylene glycol |
| الوصف: | Antibody therapies are typically based on high-concentration formulations that need to be administered subcutaneously. These conditions induce several challenges, inter alia a viscosity suitable for injection, sufficient solution stability, and preservation of molecular function. To obtain systematic insights into the molecular factors, we study the dynamics on the molecular level under strongly varying solution conditions. In particular, we use solutions of antibodies with poly(ethylene glycol), in which simple cooling from room temperature to freezing temperatures induces a transition from a well-dispersed solution into a phase-separated and macroscopically arrested system. Using quasi-elastic neutron scattering during in situ cooling ramps and in prethermalized measurements, we observe a strong decrease in antibody diffusion, while internal flexibility persists to a significant degree, thus ensuring the movement necessary for the preservation of molecular function. These results are relevant for a more dynamic understanding of antibodies in high-concentration formulations, which affects the formation of transient clusters governing the solution viscosity. |
| وصف الملف: | application/pdf |
| تدمد: | 1543-8392 1543-8384 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4e5237ece26dd0f1adfd4269b79350e https://doi.org/10.1021/acs.molpharmaceut.1c00555 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d4e5237ece26dd0f1adfd4269b79350e |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15438392 15438384 |
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