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The higher-order structure (HOS) of protein therapeutics has been confirmed as a critical quality parameter. In this study, we compared 2D H-C ALSOFAST-HMQC NMR spectra with immunochemical ELISA-based analysis to evaluate their sensitivity in assessing the HOS of a potent human monoclonal antibody (mAb) for the treatment of coronavirus disease 2019 (COVID-19). The study confirmed that the methyl region of the 2D H-C NMR spectrum is sensitive to changes in the secondary and tertiary structure of the mAb, more than ELISA immunoassay. Because of its highly detailed level of characterization (i.e., many H-C cross-peaks are used for statistical comparability), the NMR technique also provided a more informative outcome for the product characterization of biopharmaceuticals. This NMR approach represents a powerful tool in assessing the overall higher-order structural integrity of mAb as an alternative to conventional immunoassays.
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http://dx.doi.org/10.3390/pharmaceutics14101981 | DOI Listing |
MAbs
December 2025
Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
The analytical comparability of biologic products and their biosimilars, including higher-order structure (HOS) assessment, ensures product quality and is required for regulatory approval. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to evaluate the HOS of Humira (adalimumab) and its biosimilars under normal and photo-stressed conditions. Under normal conditions, 1D and 2D NMR spectra showed strong structural similarity among all products.
View Article and Find Full Text PDFBMB Rep
September 2025
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
DNA, a large molecule located in the nucleus, carries essential genetic information, including gene loci and cis-regulatory elements. Despite its extensive length, DNA is compactly stored within the limited space of the nucleus due to its hierarchical three-dimensional (3D) organization. In this structure, DNA is organized into territories known as topologically associated domains (TADs).
View Article and Find Full Text PDFNeuropsychologia
September 2025
Icelandic Vision Lab, Department of Psychology, University of Iceland, Saemundargata 2, 102, Reykjavik, Iceland.
Developmental dyslexia is a disorder marked by difficulties in reading, spelling, and connecting sounds to written language. The high-level visual dysfunction hypothesis suggests these difficulties may partially arise from abnormalities in high-level visual cognition such as the ability to integrate visual input for higher-order cognitive functions such as reading. Here we examined adult (mean age = 35) dyslexic readers' neural functioning as they recognized identities of nonlinguistic visual objects, specifically houses and faces.
View Article and Find Full Text PDFAnal Biochem
September 2025
School of Computer Science and Engineering, Southeast University, Nanjing 210000, China.
In the complex process of gene expression and regulation, RNA-binding proteins occupy a pivotal position for RNA. Accurate prediction of RNA-protein binding sites can help researchers better understand RNA-binding proteins and their related mechanisms. And prediction techniques based on machine learning algorithms are both cost-effective and efficient in identifying these binding sites.
View Article and Find Full Text PDFRNA can fold to form complex three-dimensional tertiary structures, with large roles in RNA biology. However, accurate discovery of motifs that form true tertiary structures remains an unsolved challenge. Here we demonstrate that at rare but distinctive sites, RNA tertiary folding creates electronegative pockets that undergo selective chemistry with a small positively-charged chemical probe, trimethyloxonium (TMO).
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