Protein Engineering and HDX Identify Structural Regions of G-CSF Critical to Its Stability and Aggregation.

Deuterium Exchange Measurement / methods Excipients / chemistry Granulocyte Colony-Stimulating Factor / chemistry Hydrogen Deuterium Exchange-Mass Spectrometry Protein Conformation Protein Engineering Proteins
aggregation formulation intermediate protein engineering stability

Journal

Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791

Informations de publication

Date de publication:
07 02 2022
Historique:
pubmed: 31 12 2021
medline: 5 4 2022
entrez: 30 12 2021
Statut: ppublish

Résumé

The protein engineering and formulation of therapeutic proteins for prolonged shelf-life remain a major challenge in the biopharmaceutical industry. Understanding the influence of mutations and formulations on the protein structure and dynamics could lead to more predictive approaches to their improvement. Previous intrinsic fluorescence analysis of the chemically denatured granulocyte colony-stimulating factor (G-CSF) suggested that loop AB could subtly reorganize to form an aggregation-prone intermediate state. Hydrogen deuterium exchange mass spectrometry (HDX-MS) has also revealed that excipient binding increased the thermal unfolding transition midpoint (

Identifiants

DOI: 10.1021/acs.molpharmaceut.1c00754 PMID: 34965730
pubmed: 34965730
doi: 10.1021/acs.molpharmaceut.1c00754
doi:

Substances chimiques

Excipients 0
Proteins 0
Granulocyte Colony-Stimulating Factor 143011-72-7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

616-629

Auteurs

Victoria E Wood (VE)

Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, U.K.

Kate Groves (K)

National Measurement Laboratory at LGC Ltd, Queens Road, Teddington TW11 0LY, U.K.
ORCID: 0000-0001-9207-6392

Lok Man Wong (LM)

Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, U.K.

Luyan Kong (L)

Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, U.K.

Christopher Bird (C)

National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, U.K.

Meenu Wadhwa (M)

National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, U.K.

Milena Quaglia (M)

National Measurement Laboratory at LGC Ltd, Queens Road, Teddington TW11 0LY, U.K.

Paul Matejtschuk (P)

National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, U.K.

Paul A Dalby (PA)

Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, U.K.
ORCID: 0000-0002-0980-8167

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Mesure d'échange de deutérium › Protein Engineering and HDX Identify...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Excipients pharmaceutiques › Excipients › Protein Engineering and HDX Identify...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de croissance hématopoïétique › Facteurs de stimulation des colonies › Facteur de stimulation des colonies de granulocytes › Protein Engineering and HDX Identify...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Échange hydrogène/deutérium couplé à la spectrométrie de masse › Protein Engineering and HDX Identify...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Protein Engineering and HDX Identify...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Ingénierie des protéines › Protein Engineering and HDX Identify...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protein Engineering and HDX Identify...