title: Effect of arginine on protein aggregation studied by fluorescence correlation spectroscopy and other biophysical methods.
abstract: 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.
authors.affiliation: Structural Biology and Bioinformatics, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4, Raja S. C. Mullick Road, Kolkata 700032, India.
authors.forename: Ranendu
authors.initials: R
authors.lastname: Ghosh
authors.forename: Sunny
authors.initials: S
authors.lastname: Sharma
authors.forename: Krishnananda
authors.initials: K
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000502:physiology; D002417:Cattle; D002942:Circular Dichroism; D015180:Electrophoresis, Gel, Two-Dimensional; D006358:Hot Temperature; D008027:Light; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D012542:Scattering, Radiation; D012710:Serum Albumin, Bovine / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence / Q000379:methods; D014461:Ultracentrifugation
chemical_list: D012710:Serum Albumin, Bovine; D001120:Arginine