ABSTRACT

Most biopharmaceuticals are proteins or protein conjugates and are considered to be biopolymers. Proteins have a unique conformation in solution, which is the product of diverse covalent and noncovalent interactions. It is generally accepted that the primary structure of proteins dictates their secondary and tertiary structures, and the nal conformation is stabilized by the aforementioned covalent and noncovalent interactions. These interactions can be intramolecular or intermolecular; intramolecular interactions dominate at low protein concentrations, whereas intermolecular interactions are more signicant at higher protein concentrations, where such forces are involved in processes such as aggregation. This is not to say that intermolecular interactions are not important at low protein concentrations; however, such interactions are usually driven by specic multivalent interactions.1