2D 1HN, 15N Correlated NMR Methods at Natural Abundance for Obtaining Structural Maps and Statistical Comparability of Monoclonal Antibodies View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-02

AUTHORS

Luke W. Arbogast, Robert G. Brinson, Trina Formolo, J. Todd Hoopes, John P. Marino

ABSTRACT

PURPOSE: High-resolution nuclear magnetic resonance spectroscopy (NMR) provides a robust approach for producing unique spectral signatures of protein higher order structure at atomic resolution. Such signatures can be used as a tool to establish consistency of protein folding for the assessment of monoclonal antibody (mAb) drug quality and comparability. METHODS: Using the NIST monoclonal antibody (NISTmAb) and a commercial-sourced polyclonal antibody, both IgG1κ isotype, we apply 2D NMR methods at natural abundance for the acquisition and unbiased statistical analysis of (1)H(N) -(15)N correlated spectra of intact antibody (Ab) and protease-cleaved Fab and Fc fragments. RESULTS: The study demonstrates the feasibility of applying 2D NMR techniques to Abs and the precision with which these methods can be used to map structure and establish comparability between samples at atomic resolution. CONCLUSIONS: The statistical analyses suggests that, within the limit of detection, no significant structural differences are observed between the Fab and Fc domains of each respective intact Ab and its corresponding fragments. Discrimination between dissimilar species, such as between the Fab domains of both Abs or between the glycosylated and deglycosylated Fc domains, was further demonstrated. As such, these methods should find general utility for the assessment of mAb higher order structure. More... »

PAGES

462-475

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11095-015-1802-3

DOI

http://dx.doi.org/10.1007/s11095-015-1802-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1038890267

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26453189


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s11095-015-1802-3'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s11095-015-1802-3'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s11095-015-1802-3'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s11095-015-1802-3'


 

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