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

摘要

Arginine has been used extensively as an excipient in the formulation development of proteinbasednbiopharmaceuticals. We investigate the role of arginine in suppressing protein aggregation and itsnmechanism by using bovine serum albumin as a model system. By using sedimentation velocity andnother analytical techniques, we show that the use of arginine inhibits temperature-induced aggregation ofnthe protein. We use fluorescence correlation spectroscopy and other spectroscopic techniques to shownthat arginine inhibits accumulation of partially folded intermediates, potentially involved in the aggregationnprocess. The hydrodynamic radii of the protein in its native, unfolded, and intermediate states have beenndetermined using fluorescence correlation spectroscopy at single-molecule resolution. A possible mechanismnof the effects of arginine and its role as an aggregation suppressor has been discussed.