title: Protein refolding using chemical refolding additives.
abstract: In laboratories and manufacturing settings, a rapid and inexpensive method for the preparation of a target protein is crucial for promoting resesrach in protein science and engineering. Inclusion-body-based protein production is a promising method because high yields are achieved in the upstream process, although the refolding of solubilized, unfolded proteins in downstream processes often leads to significantly lower yields. The most challenging problem is that the effective condition for refolding is protein dependent and is therefore difficult to select in a rational manner. Accordingly, considerable time and expense using trial-and-error approaches are often needed to increase the final protein yield. Furthermore, for certain target proteins, finding suitable conditions to achieve an adequate yield cannot be obtained by existing methods. Therefore, to convert such a troublesome refolding process into a routine one, a wide array of methods based on novel technologies and materials have been developed. These methods select refolding conditions where productive refolding dominates over unproductive aggregation in competitive refolding reactions. This review focuses on synthetic refolding additives and describes the concepts underlying the development of reported chemical additives or chemical-additive-based methods that contribute to the emergence of a universal refolding method.
authors.affiliation: Department of Chemistry & Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan. yamaguchi@bio.t.u-tokyo.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Etsushi
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Mannen
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Nagamune
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Nagamune
mesh_terms: D001709:Biotechnology; D008958:Models, Molecular; D017510:Protein Folding; D058849:Protein Refolding; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D011506:Proteins; D011994:Recombinant Proteins