Conformational stability and self-association equilibrium in biologics

Benjamin R. Clarkson, Arne Schön, Ernesto Freire

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Pages (from-to)342-347
Number of pages6
JournalDrug Discovery Today
Volume21
Issue number2
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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