NDLI: Inverse Relationship of Protein Concentration and Aggregation

Content Provider	Springer Nature Link
Author	Treuheit, Michael J. Kosky, Andrew A. Brems, David N.
Copyright Year	2002
Abstract	Purpose. To determine the effect of protein concentration on aggregation induced through quiescent shelf-life incubation or shipping-related agitation. Methods. All aggregation was measured by size-exclusion high-performance liquid chromatography. Aggregation was induced by time-dependent incubation under stationary conditions or by agitation caused by shaking, vortexing, or vibration using simulated shipping conditions. Results. Protein aggregation is commonly a second- or higher-order process that is expected to increase with higher protein concentration. As expected, for three proteins (PEG-GCSF, PEG-MGDF, and OPG-Fc) that were examined, the aggregation increased with higher protein concentration if incubated in a quiescent shelf-life setting. However, aggregation decreased with higher protein concentration if induced by an air/water interface as a result of agitation. This unexpected result may be explained by the rate-limiting effect on aggregation of the air/water interface and the critical nature of the air/water interface to protein ratio that is greatest with decreased protein concentration. The non-ionic detergent polysorbate 20 enhanced the aggregation observed in the quiescently incubated sample but abrogated the aggregation induced by the air/water interface. Conclusions. The effect of protein concentration was opposite for aggregation that resulted from quiescent shelf-life treatment compared to induction by agitation. For motionless shelf-life incubation, increased concentration of protein resulted in more aggregation. However, exposure to agitation resulted in more aggregation with decreased protein concentration. These results highlight an unexpected complexity of protein aggregation reactions.
Starting Page	511
Ending Page	516
Page Count	6
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	19
Issue Number	4
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2002-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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