Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation.
Irreversible protein aggregation is problematic in the biotechnology industry, where aggregation is encountered throughout the lifetime of a therapeutic protein, including during refolding, purification, sterilization, shipping, and storage processes. The purpose of the current review is to provide a fundamental understanding of the mechanisms by which proteins aggregate and by which varying solution conditions, such as temperature, pH, salt type, salt concentration, cosolutes, preservatives, and surfactants, affect this process.
Department of Chemical Engineering, Center for Pharmaceutical Biotechnology, ECCH 111, Campus Box 424, University of Colorado, Boulder, Colorado, USA.
Eva Y
EY
Chi
Sampathkumar
S
Krishnan
Theodore W
TW
Randolph
John F
JF
Carpenter
D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D019999:Pharmaceutical Solutions / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry*
D019999:Pharmaceutical Solutions; D011506:Proteins; D012997:Solvents; D013501:Surface-Active Agents; D014867:Water