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Assessing analytical methods to monitor isoAsp formation in monoclonal antibodies

Overview of attention for article published in Frontiers in Pharmacology, April 2014
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Title
Assessing analytical methods to monitor isoAsp formation in monoclonal antibodies
Published in
Frontiers in Pharmacology, April 2014
DOI 10.3389/fphar.2014.00087
Pubmed ID
Authors

Catherine M. Eakin, Amanda Miller, Jennifer Kerr, James Kung, Alison Wallace

Abstract

A ubiquitous post-translational modification observed in proteins is isomerization of aspartic acid to isoaspartic acid (isoAsp). This non-enzymatic post-translational modification occurs spontaneously in proteins and plays a role in aging, autoimmune response, cancer, neurodegeneration, and other diseases. Formation of isoAsp is also a significant issue for recombinant monoclonal antibody based protein therapeutics particularly when isomerization occurs in a complementarity-determining region due to potential impact to the clinical efficacy. Here, we present and compare three analytical methods to monitor and/or quantify isoAsp formation in a monoclonal antibody. The methods include two peptide map based technologies with quantitation from either UV integration or total ion peak areas, as well as an alternative approach using IdeS digestion to generate Fc/2 and Fab'2 regions, followed by hydrophobic interaction chromatography (HIC) to separate the population of Fab'2 containing an isoAsp. The level of isoAsp detected by the peptide map and the digested-HIC methods presented here show similar trends although sample throughput varies by method.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Italy 1 1%
Unknown 67 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 26 38%
Student > Doctoral Student 8 12%
Student > Ph. D. Student 7 10%
Student > Master 4 6%
Student > Bachelor 3 4%
Other 4 6%
Unknown 17 25%
Readers by discipline Count As %
Chemistry 16 23%
Agricultural and Biological Sciences 13 19%
Biochemistry, Genetics and Molecular Biology 12 17%
Pharmacology, Toxicology and Pharmaceutical Science 6 9%
Chemical Engineering 2 3%
Other 4 6%
Unknown 16 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2014.
All research outputs
#20,228,822
of 22,754,104 outputs
Outputs from Frontiers in Pharmacology
#9,979
of 16,008 outputs
Outputs of similar age
#193,553
of 227,503 outputs
Outputs of similar age from Frontiers in Pharmacology
#60
of 85 outputs
Altmetric has tracked 22,754,104 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,008 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 85 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.