Aggregation of protein therapeutics has long been a concern across different stages of manufacturing processes in the biopharmaceutical industry. It is often indicative of aberrant protein therapeutic higher-order structure. In this study, the aggregation propensity of a human Fc-fusion protein therapeutic was characterized. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was applied to examine the conformational dynamics of dimers collected from a bioreactor. HDX-MS data combined with spatial aggregation propensity calculations revealed a potential aggregation interface in the Fc domain. This study provides a general strategy for the characterization of the aggregation propensity of Fc-fusion proteins at the molecular level.Graphical Abstract.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s13361-016-1452-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Co-Localized in Amyloid Plaques Cathepsin B as a Source of Peptide Analogs Potential Drug Candidates for Alzheimer's Disease.
Biomolecules
December 2024
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, 157 01 Athens, Greece.
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by extracellular amyloid plaques, predominantly consisting of amyloid- (A) peptides. The oligomeric form of A is acknowledged as the most neurotoxic, propelling the pathological progression of AD. Interestingly, besides A, other proteins are co-localized within amyloid plaques.
View Article and Find Full Text PDFIdentification of the Highly Polymorphic Prion Protein Gene () in Frogs ).
Animals (Basel)
January 2025
Department of Biological Sciences, Andong National University, Andong 36729, Republic of Korea.
Prion diseases are fatal neurodegenerative diseases that can be transmitted by infectious protein particles, PrPs, encoded by the endogenous prion protein gene (). The origin of prion seeds is unclear, especially in non-human hosts, and this identification is pivotal to preventing the spread of prion diseases from host animals. Recently, an abnormally high amyloid propensity in prion proteins (PrPs) was found in a frog, of which the genetic variations in the gene have not been investigated.
View Article and Find Full Text PDFCell-free expression and SMA copolymer encapsulation of a functional receptor tyrosine kinase disease variant, FGFR3-TACC3.
Sci Rep
January 2025
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Despite their high clinical relevance, obtaining structural and biophysical data on transmembrane proteins has been hindered by challenges involved in their expression and extraction in a homogeneous, functionally-active form. The inherent enzymatic activity of receptor tyrosine kinases (RTKs) presents additional challenges. Oncogenic fusions of RTKs with heterologous partners represent a particularly difficult-to-express protein subtype due to their high flexibility, aggregation propensity and the lack of a known method for extraction within the native lipid environment.
View Article and Find Full Text PDFPsoriasis increases the risk of Sjögren's syndrome: evidence from a propensity score-matched cohort study and transcriptomic analysis.
BMC Med
January 2025
Department of Rheumatology and Immunology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Despite the well-documented immune dysregulation in both psoriasis and Sjögren's syndrome (SS), the specific link between these two autoimmune diseases has not been extensively explored. The present study aims to investigate the impact of psoriasis on the risk of SS.
Methods: A retrospective cohort study using TriNetX data compared SS development in patients with psoriasis and controls using propensity score matching, Kaplan-Meier curves, and Cox models.
Strategy to mitigate aggregation during Protein A chromatography and low pH virus inactivation for a nivolumab biosimilar candidate.
J Chromatogr A
January 2025
Center of Molecular Immunology, 216 Street and 15th Avenue Atabey-Siboney Playa P.O. Box 16040, Havana, 11600, Cuba. Electronic address:
Protein A chromatography represents the most prevalent methodology for the capture of monoclonal antibodies. The use of a low pH elution buffer from Protein A has been observed to contribute to product aggregation, particularly in the case of IgG4 antibodies, such as nivolumab. This paper presents a well-defined strategy for addressing this issue.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!