The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation
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 deteriora...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/11/1853 |
| _version_ | 1797508813208682496 |
|---|---|
| author | Ingrid Ramm Adrian Sanchez-Fernandez Jaeyeong Choi Christian Lang Jonas Fransson Herje Schagerlöf Marie Wahlgren Lars Nilsson |
| author_facet | Ingrid Ramm Adrian Sanchez-Fernandez Jaeyeong Choi Christian Lang Jonas Fransson Herje Schagerlöf Marie Wahlgren Lars Nilsson |
| author_sort | Ingrid Ramm |
| collection | DOAJ |
| description | 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% <i>v</i>/<i>v</i>. 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. |
| first_indexed | 2024-03-10T05:09:12Z |
| format | Article |
| id | doaj.art-9f1544ffd84b4b91b9480d507d08173d |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T05:09:12Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9f1544ffd84b4b91b9480d507d08173d2023-11-23T00:58:36ZengMDPI AGPharmaceutics1999-49232021-11-011311185310.3390/pharmaceutics13111853The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical DegradationIngrid Ramm0Adrian Sanchez-Fernandez1Jaeyeong Choi2Christian Lang3Jonas Fransson4Herje Schagerlöf5Marie Wahlgren6Lars Nilsson7Department of Food Technology, Engineering and Nutrition, Lund University, 221 00 Lund, SwedenDepartment of Food Technology, Engineering and Nutrition, Lund University, 221 00 Lund, SwedenDepartment of Food Technology, Engineering and Nutrition, Lund University, 221 00 Lund, SwedenJülich Centre for Neutron Science, Heinz Maier-Leibnitz Zentrum, 85748 Garching, GermanySOBI, Tomtebodavägen 23A, 171 65 Stockholm, SwedenDepartment of Chemical Engineering, Lund University, 221 00 Lund, SwedenDepartment of Food Technology, Engineering and Nutrition, Lund University, 221 00 Lund, SwedenDepartment of Food Technology, Engineering and Nutrition, Lund University, 221 00 Lund, SwedenThe 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% <i>v</i>/<i>v</i>. 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.https://www.mdpi.com/1999-4923/13/11/1853pharmaceutical proteinsliquid formulationglycerolprotein stabilitychemical degradationchemical stability |
| spellingShingle | Ingrid Ramm Adrian Sanchez-Fernandez Jaeyeong Choi Christian Lang Jonas Fransson Herje Schagerlöf Marie Wahlgren Lars Nilsson The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation Pharmaceutics pharmaceutical proteins liquid formulation glycerol protein stability chemical degradation chemical stability |
| title | The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation |
| title_full | The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation |
| title_fullStr | The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation |
| title_full_unstemmed | The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation |
| title_short | The Impact of Glycerol on an Affibody Conformation and Its Correlation to Chemical Degradation |
| title_sort | impact of glycerol on an affibody conformation and its correlation to chemical degradation |
| topic | pharmaceutical proteins liquid formulation glycerol protein stability chemical degradation chemical stability |
| url | https://www.mdpi.com/1999-4923/13/11/1853 |
| work_keys_str_mv | AT ingridramm theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT adriansanchezfernandez theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT jaeyeongchoi theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT christianlang theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT jonasfransson theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT herjeschagerlof theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT mariewahlgren theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT larsnilsson theimpactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT ingridramm impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT adriansanchezfernandez impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT jaeyeongchoi impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT christianlang impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT jonasfransson impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT herjeschagerlof impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT mariewahlgren impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation AT larsnilsson impactofglycerolonanaffibodyconformationanditscorrelationtochemicaldegradation |