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RAP opportunity at National Institute of Standards and Technology     NIST

High-Resolution Nuclear Magnetic Resonance (NMR) Spectroscopic Measurements for 3D Structural “Finger-Printing” of Biological Therapeutics


Material Measurement Laboratory, Biomolecular Measurement Division

opportunity location
50.64.51.B8485 Gaithersburg, MD

NIST only participates in the February and August reviews.


name email phone
Robert Goodwin Brinson 240.314.6336


In contrast to small molecule therapeutics, protein biologics are complex and require higher-order folding of the primary sequence (i.e., tertiary structure) for therapeutic function. While correct folding of a protein biologic is critical for drug efficacy, misfolding may impact drug safety by eliciting unwanted immune and/or other off-target responses. High-resolution measurements of the structure(s) of protein therapeutics can therefore provide an important tool for establishing consistency in drug manufacturing, for detecting drug product changes resulting from modifications in the manufacturing process, and for comparing a biosimilar to an innovator reference product. Biological therapeutics is currently characterized by low resolution techniques like CD, gel filtration, and light scattering. However, detailed analysis of biologics is quite limited using these approaches. In contrast, nuclear magnetic resonance (NMR) is a high resolution and information-rich technique that is highly sensitive to molecular structure alterations that result from mutations, misfoldings, or other contaminants. Research will focus on developing NMR as a robust spectroscopic approach for obtaining structural 'fingerprints' of the bioactive form of protein therapeutics, as well as detect variants, at atomic resolution. The research will focus on a variety of targets, including carbohydrates, recombinant proteins, glycoproteins, and monoclonal antibodies.



Arbogast LW, et al: 2D 1HN, 15N Correlated NMR Methods at Natural Abundance for Obtaining Structural Maps and Statistical Comparability of Monoclonal Antibodies. Pharmaceutical Research 33: 462-475, 2016

Ghasriani H, et al: Precision and Robustness of 2D-NMR for Structure and Assessment of Filgrastim Biosimilars. Nature Biotechnology 34: 139-141, 2016

Arbogast LW, Brinson RG, Marino JP: Application of Natural Isotopic Abundance 1H-13C and 1H-15N Correlated Two-Dimensional NMR for Evaluation of the Structure of Protein Therapeutics. Methods in Enzymology, in "Methods in Enzymology". Kelman Z, editor: Isotope Labeling of Biomolecules-Applications, 566 Burlington, VT: Academic Press, 2016, 3-34

Marino JP, et al: Emerging Technologies to Assess the Higher-Order Structure of Monoclonal Antibodies, in "Current, State of the Art, and Emerging Technologies for the Analysis of Monoclonal Antibodies". Schiel J, Borisov, O, Davis, D, editors. ACS Symposium Series 1202; Oxford University Press: Washington, DC, 2016, pp. 17- 43

Arbogast LW, Brinson RG, Marino JP: Mapping Monoclonal Antibody Structure by 2D 13C NMR at Natural Abundance. Analytical Chemistry 87: 3556-3561, 2015

Brinson RG, et al: Detection of Contaminating Enzymatic Activity in Plant-Derived Recombinant Biotechnology Products. Analytical Chemistry 86: 11508-11512, 2014


key words
Nuclear magnetic resonance (NMR); Biotherapeutics protein structure; Glycoproteins; Monoclonal antibodies; Biosimilars;


Citizenship:  Open to U.S. citizens
Level:  Open to Postdoctoral applicants


Base Stipend Travel Allotment Supplementation
$82,764.00 $3,000.00
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