title: Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids.
abstract: The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytical techniques that are commonly used to characterize protein structure, dynamics and conformation in lyophilized solids. The review also discusses the applications of recently developed mass spectrometry based methods (solid-state hydrogen deuterium exchange mass spectrometry (ssHDX-MS) and solid-state photolytic labeling mass spectrometry (ssPL-MS)) and their ability to study proteins in the solid-state at high resolution.
authors.forename: Balakrishnan S
authors.initials: BS
authors.lastname: Moorthy
authors.forename: Lavanya K
authors.initials: LK
authors.lastname: Iyer
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, Room 124D, West Lafayette, IN 47907-2091. topp@purdue.edu.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Topp
mesh_terms: D002626:Chemistry, Pharmaceutical; D005612:Freeze Drying / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins