Effect of Arginine on Protein Aggregation Studied by Fluorescence Correlation Spectroscopy and Other Biophysical Methods

Arginine has been used extensively as an excipient in the formulation development of protein-based biopharmaceuticals. We investigate the role of arginine in suppressing protein aggregation and its mechanism by using bovine serum albumin as a model system. By using sedimentation velocity and other a...

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Bibliographic Details
Published in:Biochemistry (Easton) 2009-02, Vol.48 (5), p.1135-1143
Main Authors: Ghosh, Ranendu, Sharma, Sunny, Chattopadhyay, Krishnananda
Format: Article
Language:English
Subjects:
Animals
Arginine - chemistry
Arginine - physiology
Cattle
Circular Dichroism
Electrophoresis, Gel, Two-Dimensional
Hot Temperature
Light
Protein Conformation
Protein Folding
Protein Stability
Scattering, Radiation
Serum Albumin, Bovine - antagonists & inhibitors
Serum Albumin, Bovine - chemistry
Serum Albumin, Bovine - metabolism
Spectrometry, Fluorescence - methods
Ultracentrifugation
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Summary:Arginine has been used extensively as an excipient in the formulation development of protein-based biopharmaceuticals. We investigate the role of arginine in suppressing protein aggregation and its mechanism by using bovine serum albumin as a model system. By using sedimentation velocity and other analytical techniques, we show that the use of arginine inhibits temperature-induced aggregation of the protein. We use fluorescence correlation spectroscopy and other spectroscopic techniques to show that arginine inhibits accumulation of partially folded intermediates, potentially involved in the aggregation process. The hydrodynamic radii of the protein in its native, unfolded, and intermediate states have been determined using fluorescence correlation spectroscopy at single-molecule resolution. A possible mechanism of the effects of arginine and its role as an aggregation suppressor has been discussed.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi802065j