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Hydration-Induced Structural Changes in the Solid State of Protein : A SAXS/WAXS Study on Lysozyme

Phan-Xuan, Tuan ; Bogdanova, Ekaterina ; Millqvist Fureby, Anna ; Fransson, Jonas ; Terry, Ann E. LU and Kocherbitov, Vitaly LU (2020) In Molecular Pharmaceutics 17(9). p.3246-3258
Abstract

The stability of biologically produced pharmaceuticals is the limiting factor to various applications, which can be improved by formulation in solid-state forms, mostly via lyophilization. Knowledge about the protein structure at the molecular level in the solid state and its transition upon rehydration is however scarce, and yet it most likely affects the physical and chemical stability of the biological drug. In this work, synchrotron small- and wide-angle X-ray scattering (SWAXS) are used to characterize the structure of a model protein, lysozyme, in the solid state and its structural transition upon rehydration to the liquid state. The results show that the protein undergoes distortion upon drying to adopt structures that can... (More)

The stability of biologically produced pharmaceuticals is the limiting factor to various applications, which can be improved by formulation in solid-state forms, mostly via lyophilization. Knowledge about the protein structure at the molecular level in the solid state and its transition upon rehydration is however scarce, and yet it most likely affects the physical and chemical stability of the biological drug. In this work, synchrotron small- and wide-angle X-ray scattering (SWAXS) are used to characterize the structure of a model protein, lysozyme, in the solid state and its structural transition upon rehydration to the liquid state. The results show that the protein undergoes distortion upon drying to adopt structures that can continuously fill the space to remove the protein-air interface that may be formed upon dehydration. Above a hydration threshold of 35 wt %, the native structure of the protein is recovered. The evolution of SWAXS peaks as a function of water content in a broad range of concentrations is discussed in relation to the structural changes in the protein. The findings presented here can be used for the design and optimization of solid-state formulations of proteins with improved stability.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biotherapeutics, dehydration, distorted structure, hydration, small- and wide-angle X-ray scattering, solid-state protein
in
Molecular Pharmaceutics
volume
17
issue
9
pages
13 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85090505313
  • pmid:32787275
ISSN
1543-8392
DOI
10.1021/acs.molpharmaceut.0c00351
language
English
LU publication?
yes
id
7ff5ba03-efb9-48fe-a1b2-f92988efac41
date added to LUP
2020-09-29 13:36:52
date last changed
2024-03-05 09:41:52
@article{7ff5ba03-efb9-48fe-a1b2-f92988efac41,
  abstract     = {{<p>The stability of biologically produced pharmaceuticals is the limiting factor to various applications, which can be improved by formulation in solid-state forms, mostly via lyophilization. Knowledge about the protein structure at the molecular level in the solid state and its transition upon rehydration is however scarce, and yet it most likely affects the physical and chemical stability of the biological drug. In this work, synchrotron small- and wide-angle X-ray scattering (SWAXS) are used to characterize the structure of a model protein, lysozyme, in the solid state and its structural transition upon rehydration to the liquid state. The results show that the protein undergoes distortion upon drying to adopt structures that can continuously fill the space to remove the protein-air interface that may be formed upon dehydration. Above a hydration threshold of 35 wt %, the native structure of the protein is recovered. The evolution of SWAXS peaks as a function of water content in a broad range of concentrations is discussed in relation to the structural changes in the protein. The findings presented here can be used for the design and optimization of solid-state formulations of proteins with improved stability.</p>}},
  author       = {{Phan-Xuan, Tuan and Bogdanova, Ekaterina and Millqvist Fureby, Anna and Fransson, Jonas and Terry, Ann E. and Kocherbitov, Vitaly}},
  issn         = {{1543-8392}},
  keywords     = {{biotherapeutics; dehydration; distorted structure; hydration; small- and wide-angle X-ray scattering; solid-state protein}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{3246--3258}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Molecular Pharmaceutics}},
  title        = {{Hydration-Induced Structural Changes in the Solid State of Protein : A SAXS/WAXS Study on Lysozyme}},
  url          = {{http://dx.doi.org/10.1021/acs.molpharmaceut.0c00351}},
  doi          = {{10.1021/acs.molpharmaceut.0c00351}},
  volume       = {{17}},
  year         = {{2020}},
}