Technical Decision Making with Higher Order Structure Data: Higher Order Structure Characterization During Protein Therapeutic Candidate Screening

2015 ◽  
Vol 104 (4) ◽  
pp. 1533-1538 ◽  
Author(s):  
Yijia Jiang ◽  
Cynthia Li ◽  
Jenny Li ◽  
John P. Gabrielson ◽  
Jie Wen
Keyword(s):  
Decision Making ◽  
Structure Data ◽  
Higher Order ◽  
Structure Characterization ◽  
Order Structure ◽  
Protein Therapeutic

Technical Decision Making With Higher Order Structure Data: Perspectives on Higher Order Structure Characterization From the Biopharmaceutical Industry

2016 ◽  
Vol 105 (12) ◽  
pp. 3465-3470 ◽  
Author(s):  
William F. Weiss ◽  
John P. Gabrielson ◽  
Wasfi Al-Azzam ◽  
Guodong Chen ◽  
Darryl L. Davis ◽  
...  
Keyword(s):  
Decision Making ◽  
Structure Data ◽  
Higher Order ◽  
Structure Characterization ◽  
Order Structure ◽  
Biopharmaceutical Industry

Current Trends in Biotherapeutic Higher Order Structure Characterization by Irreversible Covalent Footprinting Mass Spectrometry

2019 ◽  
Vol 26 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Natalie K. Garcia ◽  
Galahad Deperalta ◽  
Aaron T. Wecksler
Keyword(s):  
Mass Spectrometry ◽  
Protein Structure ◽  
Protein Interactions ◽  
Quaternary Structure ◽  
Solvent Accessibility ◽  
Higher Order ◽  
Structure Characterization ◽  
Order Structure ◽  
Protein Footprinting ◽  
Wide Range

Background: Biotherapeutics, particularly monoclonal antibodies (mAbs), are a maturing class of drugs capable of treating a wide range of diseases. Therapeutic function and solutionstability are linked to the proper three-dimensional organization of the primary sequence into Higher Order Structure (HOS) as well as the timescales of protein motions (dynamics). Methods that directly monitor protein HOS and dynamics are important for mapping therapeutically relevant protein-protein interactions and assessing properly folded structures. Irreversible covalent protein footprinting Mass Spectrometry (MS) tools, such as site-specific amino acid labeling and hydroxyl radical footprinting are analytical techniques capable of monitoring the side chain solvent accessibility influenced by tertiary and quaternary structure. Here we discuss the methodology, examples of biotherapeutic applications, and the future directions of irreversible covalent protein footprinting MS in biotherapeutic research and development. Conclusion: Bottom-up mass spectrometry using irreversible labeling techniques provide valuable information for characterizing solution-phase protein structure. Examples range from epitope mapping and protein-ligand interactions, to probing challenging structures of membrane proteins. By paring these techniques with hydrogen-deuterium exchange, spectroscopic analysis, or static-phase structural data such as crystallography or electron microscopy, a comprehensive understanding of protein structure can be obtained.

scholarly journals Chemometric outlier classification of 2D-NMR spectra to enable higher order structure characterization of protein therapeutics

2020 ◽  
Vol 199 ◽  
pp. 103973 ◽  
Author(s):  
David A. Sheen ◽  
Vincent K. Shen ◽  
Robert G. Brinson ◽  
Luke W. Arbogast ◽  
John P. Marino ◽  
...  
Keyword(s):  
Nmr Spectra ◽  
2D Nmr ◽  
Higher Order ◽  
Protein Therapeutics ◽  
Structure Characterization ◽  
Order Structure ◽  
2D Nmr Spectra
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