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The impact of glycerol on an affibody conformation and its correlation to chemical degradation

Ramm, Ingrid LU ; Sanchez-Fernandez, Adrian LU orcid ; Choi, Jaeyeong LU orcid ; Lang, Christian ; Fransson, Jonas LU ; Schagerlöf, Herje LU ; Wahlgren, Marie LU orcid and Nilsson, Lars LU (2021) In Pharmaceutics 13(11).
Abstract

The addition of glycerol to protein solutions is often used to hinder the aggregation and denaturation of proteins. However, it is not a generalised practice against chemical degradation reactions. The chemical degradation of proteins, such as deamidation and isomerisation, is an important deteriorative mechanism that leads to a loss of functionality of pharmaceutical proteins. Here, the influence of glycerol on the chemical degradation of a protein and its correlation to glycerol-induced conformational changes is presented. The time-dependent chemical degradation of a pharmaceutical protein, GA-Z, in the absence and presence of glycerol was investigated in a stability study. The effect of glycerol on protein conformation and... (More)

The addition of glycerol to protein solutions is often used to hinder the aggregation and denaturation of proteins. However, it is not a generalised practice against chemical degradation reactions. The chemical degradation of proteins, such as deamidation and isomerisation, is an important deteriorative mechanism that leads to a loss of functionality of pharmaceutical proteins. Here, the influence of glycerol on the chemical degradation of a protein and its correlation to glycerol-induced conformational changes is presented. The time-dependent chemical degradation of a pharmaceutical protein, GA-Z, in the absence and presence of glycerol was investigated in a stability study. The effect of glycerol on protein conformation and oligomerisation was characterised using asymmetric field-flow fractionation and small-angle neutron scattering in a wide glycerol concentration range of 0–90% v/v. The results from the stability study were connected to the observed glycerol-induced conformational changes in the protein. A correlation between protein conformation and the protective effect of glycerol against the degradation reactions deamidation, isomerisation, and hydrolysis was found. The study reveals that glycerol induces conformational changes of the protein, which favour a more compact and chemically stable state. It is also shown that the conformation can be changed by other system properties, e.g., protein concentration, leading to increased chemical stability.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chemical degradation, Chemical stability, Glycerol, Liquid formulation, Pharmaceutical proteins, Protein conformation, Protein stability
in
Pharmaceutics
volume
13
issue
11
article number
1853
pages
14 pages
publisher
MDPI AG
external identifiers
  • pmid:34834267
  • scopus:85118779868
ISSN
1999-4923
DOI
10.3390/pharmaceutics13111853
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
id
71241049-01c9-4f8f-9b08-de0fc563713d
date added to LUP
2021-11-17 21:57:05
date last changed
2024-06-29 21:40:41
@article{71241049-01c9-4f8f-9b08-de0fc563713d,
  abstract     = {{<p>The addition of glycerol to protein solutions is often used to hinder the aggregation and denaturation of proteins. However, it is not a generalised practice against chemical degradation reactions. The chemical degradation of proteins, such as deamidation and isomerisation, is an important deteriorative mechanism that leads to a loss of functionality of pharmaceutical proteins. Here, the influence of glycerol on the chemical degradation of a protein and its correlation to glycerol-induced conformational changes is presented. The time-dependent chemical degradation of a pharmaceutical protein, GA-Z, in the absence and presence of glycerol was investigated in a stability study. The effect of glycerol on protein conformation and oligomerisation was characterised using asymmetric field-flow fractionation and small-angle neutron scattering in a wide glycerol concentration range of 0–90% v/v. The results from the stability study were connected to the observed glycerol-induced conformational changes in the protein. A correlation between protein conformation and the protective effect of glycerol against the degradation reactions deamidation, isomerisation, and hydrolysis was found. The study reveals that glycerol induces conformational changes of the protein, which favour a more compact and chemically stable state. It is also shown that the conformation can be changed by other system properties, e.g., protein concentration, leading to increased chemical stability.</p>}},
  author       = {{Ramm, Ingrid and Sanchez-Fernandez, Adrian and Choi, Jaeyeong and Lang, Christian and Fransson, Jonas and Schagerlöf, Herje and Wahlgren, Marie and Nilsson, Lars}},
  issn         = {{1999-4923}},
  keywords     = {{Chemical degradation; Chemical stability; Glycerol; Liquid formulation; Pharmaceutical proteins; Protein conformation; Protein stability}},
  language     = {{eng}},
  number       = {{11}},
  publisher    = {{MDPI AG}},
  series       = {{Pharmaceutics}},
  title        = {{The impact of glycerol on an affibody conformation and its correlation to chemical degradation}},
  url          = {{http://dx.doi.org/10.3390/pharmaceutics13111853}},
  doi          = {{10.3390/pharmaceutics13111853}},
  volume       = {{13}},
  year         = {{2021}},
}