| Autor: |
Nicholas R, Larson, Yangjie, Wei, Thayana Araújo, Cruz, Reza, Esfandiary, Cavan K, Kalonia, M Laird, Forrest, C Russell, Middaugh |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Pharmaceutical Sciences. 112:680-690 |
| ISSN: |
0022-3549 |
| DOI: |
10.1016/j.xphs.2022.10.017 |
| Popis: |
Liquid-liquid phase separation is a phenomenon within biology whereby proteins can separate into dense and more dilute phases with distinct properties. Three antibodies that undergo liquid-liquid phase separation were characterized in the protein-rich and protein-poor phases. In comparison to the protein-poor phase, the protein-rich phase demonstrates more blue-shift tryptophan emissions and red-shifted amide I absorbances. Large changes involving conformational isomerization around disulfide bonds were observed using Raman spectroscopy. Amide I and protein fluorescence differences between the phases persisted to temperatures above the critical temperature but ceased at the temperature at which aggregation occurred. In addition, large changes occurred in the structural organization of water molecules within the protein-rich phase for all three antibodies. It is hypothesized that as the proteins have the same chemical potential in both phases, the protein viscosity is higher in the protein-rich phase resulting in slowed diffusion dependent protein aggregation in this phase. For all three antibodies we performed accelerated stability studies and found that the protein-rich phase aggregated at the same rate or slower than the protein-poor phase. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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