title: On the relationship between conformation and stability in solid pharmaceutical protein formulations.
abstract: Long-term stability is critical in the successful development of pharmaceuticals, including macromolecular ones, such as proteins. Due to the relative instability of aqueous solutions of proteins, they are typically stores in a freeze-dried (lyophilized) state. However, proteins reversibly (and sometimes even irreversibly) denature upon lyophilization and consequently adopt conformations markedly distinct from the native ones. This phenomenon may profoundly affect deleterious processes in lyophilized proteins, e.g. moisture-induced aggregation, as illustrated in this review with bovine serum and recombinant human albumins.
authors.affiliation: Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. klibanov@mit.edu
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Klibanov
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Schefiliti
mesh_terms: D000418:Albumins / Q000737:chemistry; D000818:Animals; D001709:Biotechnology / Q000379:methods; D002417:Cattle; D004220:Disulfides; D004355:Drug Stability; D005612:Freeze Drying; D006801:Humans; D008968:Molecular Conformation; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds
chemical_list: D000418:Albumins; D004220:Disulfides; D013438:Sulfhydryl Compounds