title: Therapeutic protein aggregation: mechanisms, design, and control.
abstract: Although it is well known that proteins are only marginally stable in their folded states, it is often less well appreciated that most proteins are inherently aggregation-prone in their unfolded or partially unfolded states, and the resulting aggregates can be extremely stable and long-lived. For therapeutic proteins, aggregates are a significant risk factor for deleterious immune responses in patients, and can form via a variety of mechanisms. Controlling aggregation using a mechanistic approach may allow improved design of therapeutic protein stability, as a complement to existing design strategies that target desired protein structures and function. Recent results highlight the importance of balancing protein environment with the inherent aggregation propensities of polypeptide chains.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA. Electronic address: cjr@udel.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Roberts
mesh_terms: D001702:Biopharmaceutics; D001709:Biotechnology; D006801:Humans; D008958:Models, Molecular; D066329:Protein Aggregates; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D066329:Protein Aggregates; D011506:Proteins
keywords: computational design; protein aggregation; protein interactions; protein stability