title: Conformational stability and self-association equilibrium in biologics.
abstract: Biologics exist in equilibrium between native, partially denatured, and denatured conformational states. The population of any of these states is dictated by their Gibbs energy and can be altered by changes in physical and solution conditions. Some conformations have a tendency to self-associate and aggregate, an undesirable phenomenon in protein therapeutics. Conformational equilibrium and self-association are linked thermodynamic functions. Given that any associative reaction is concentration dependent, conformational stability studies performed at different protein concentrations can provide early clues to future aggregation problems. This analysis can be applied to the selection of protein variants or the identification of better formulation solutions. In this review, we discuss three different aggregation situations and their manifestation in the observed conformational equilibrium of a protein.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Clarkson
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Arne
authors.initials: A
authors.lastname: Schön
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: ef@jhu.edu.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Freire
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D001688:Biological Products; D011506:Proteins