title: Chemical degradation of proteins in the solid state with a focus on photochemical reactions.
abstract: Protein pharmaceuticals comprise an increasing fraction of marketed products but the limited solution stability of proteins requires considerable research effort to prepare stable formulations. An alternative is solid formulation, as proteins in the solid state are thermodynamically less susceptible to degradation. Nevertheless, within the time of storage a large panel of kinetically controlled degradation reactions can occur such as, e.g., hydrolysis reactions, the formation of diketopiperazine, condensation and aggregation reactions. These mechanisms of degradation in protein solids are relatively well covered by the literature. Considerably less is known about oxidative and photochemical reactions of solid proteins. This review will provide an overview over photolytic and non-photolytic degradation reactions, and specially emphasize mechanistic details on how solid structure may affect the interaction of protein solids with light.
authors.affiliation: Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mozziconacci
authors.affiliation: Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, KS 66047, USA. Electronic address: schoneic@ku.edu.
authors.forename: Christian
authors.initials: C
authors.lastname: Schöneich
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D000067917:Cloud Computing; D006801:Humans; D006868:Hydrolysis; D008027:Light; D055668:Photochemical Processes; D055550:Protein Stability; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins
keywords: Formulation; Light; Photochemistry; Protein; Solid; Stability; Stress