TY  - JOUR
AU  - Ramm, Ingrid
AU  - Sanchez-Fernandez, Adrian
AU  - Choi, Jaeyeong
AU  - Lang, Christian
AU  - Schagerlöf, Herje
AU  - Wahlgren, Marie
AU  - Nilsson, Lars
TI  - The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation
JO  - Pharmaceutics
VL  - 13
IS  - 11
SN  - 1999-4923
CY  - Basel
PB  - MDPI
M1  - FZJ-2021-05392
SP  - 1853 -
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 34834267
UR  - <Go to ISI:>//WOS:000792960900014
DO  - DOI:10.3390/pharmaceutics13111853
UR  - https://juser.fz-juelich.de/record/903752
ER  -