Journal Article

FZJ-2021-05392

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation

Ramm, I. (Corresponding author) ; Sanchez-Fernandez, A. ; Choi, J. ; Lang, C.FZJ* ; Schagerlöf, H. ; Wahlgren, M. ; Nilsson, L.

2021
MDPI Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/29574  doi:10.3390/pharmaceutics13111853

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 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.

Keyword(s): Polymers, Soft Nano Particles and Proteins (1st) ; Soft Condensed Matter (2nd) ; Biology (2nd)

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Contributing Institute(s):

1. JCNS-FRM-II (JCNS-FRM-II)
2. Neutronenstreuung (JCNS-1)
3. JCNS-4 (JCNS-4)
4. Heinz Maier-Leibnitz Zentrum (MLZ)

Research Program(s):

1. 6G4 - Jülich Centre for Neutron Research (JCNS) (FZJ) (POF4-6G4) (POF4-6G4)
2. 632 - Materials – Quantum, Complex and Functional Materials (POF4-632) (POF4-632)

Experiment(s):

1. KWS-2: Small angle scattering diffractometer (NL3ao)

Appears in the scientific report 2021

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