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Polyphenolic disaccharides endow proteins with unusual resistance to aggregation
Author(s) -
Ladiwala Ali Reza A.,
Perchiacca Joseph M.,
Fishman Zachary S.,
Bhattacharya Moumita,
Hickey Anne Marie,
Domigan Bonnie G.,
Dordick Jonathan S.,
Tessier Peter M.
Publication year - 2012
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.24460
Subject(s) - polyphenol , chemistry , naringin , aglycone , biochemistry , protein aggregation , trehalose , rutin , monosaccharide , glycoside , antioxidant , chromatography , organic chemistry
Protein aggregation is a common problem during the purification and formulation of therapeutic proteins. Here we report that polyphenolic disaccharides are unusually effective at preventing protein aggregation. We find that two polyphenolic glycosides—naringin and rutin—endow diverse proteins with the ability to unfold without aggregating when heated, as well as the ability to refold without aggregating when cooled at low glycoside concentrations (<5 mM). This extreme solubilizing activity is a synergistic combination of the glycone and aglycone moieties, as combinations of polyphenols and sugars fail to suppress aggregation. Moreover, the activity of polyphenolic disaccharides is remarkably specific since their monosaccharide counterparts (as well as other common excipients such as arginine, trehalose, and cyclodextrin) fail to prevent aggregation at similar concentrations (<25 mM). We expect that polyphenolic disaccharides will be valuable additives for enhancing the solubility of proteins in applications plagued by protein aggregation. Biotechnol. Bioeng. 2012; 109:1869–1874. © 2012 Wiley Periodicals, Inc.