Current Pharmaceutical Biotechnology

Zeno Foldes-Papp
Visiting Professor of Medical Biochemistry
HELIOS Clinical Center of Emergency Medicine
Department for Internal Medicine
Alte-Koelner-Strasse 9
D-51688 Koeln-Wipperfuerth


Effect of Additives on Protein Aggregation

Author(s): Hiroyuki Hamada, Tsutomu Arakawa and Kentaro Shiraki

Affiliation: Institute of Applied Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.

Keywords: Protein aggregation, refolding, aggregation suppressor, low-molecular-weight additive, freeze-drying, freezethawing, preferential interaction, preferential exclusion


This paper overviews solution additives that affect protein stability and aggregation during refolding, heating, and freezing processes. Solution additives are mainly grouped into two classes, i.e., protein denaturants and stabilizers. The former includes guanidine, urea, strong ionic detergents, and certain chaotropic salts; the latter includes certain amino acids, sugars, polyhydric alcohols, osmolytes, and kosmotropic salts. However, there are solution additives that are not unambiguously placed into these two classes, including arginine, certain divalent cation salts (e.g., MgCl ) and certain polyhydric alcohols (e.g., ethylene glycol). Certain non-ionic or non-detergent surfactants, ionic liquids, amino acid derivatives, polyamines, and certain amphiphilic polymers may belong to this class. They have marginal effects on protein structure and stability, but are able to disrupt protein interactions. Information on additives that do not catalyze chemical reactions nor affect protein functions helps us to design protein solutions for increased stability or reduced aggregation.

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Article Details

Page: [400 - 407]
Pages: 8
DOI: 10.2174/138920109788488941