Chapter Four Transglutaminase and Sialyltransferase Enzymatic Approaches for Polymer Conjugation to Proteins

Publication date: 2018 Source:Advances in Protein Chemistry and Structural Biology, Volume 112 Author(s): Katia Maso, Antonella Grigoletto, Gianfranco Pasut Proteins hold a central role in medicine and biology, also confirmed by the several therapeutic applications based on biologic drugs. Such therapies are of great relevance thanks to high potency and safety of proteins. Nevertheless, many proteins as therapeutics might present issues like fast kidney clearance, rapid enzymatic degradation, or immunogenicity. Such defects implicate frequent administrations or administrations at high doses of the therapeutics, thus yielding or exacerbating potential side effects. A successful technology for improving the clinical profiles of proteins is the conjugation of polymers to the protein surface. The design of a protein–polymer conjugate presents critical aspects that determine the efficacy and safety of the final product. The control over stoichiometry and conjugation site is a strict criterion on which researchers have been intensively focused during the years, in order to obtain homogeneous and batch-to-batch reproducible products. An innovative site-specific conjugation strategy relies on the use of enzymes as tools to mediate polymer conjugation. Enzymatic approaches are attractive because they allow site-selective polymer conjugation at specific protein amino acids. In these reactions, the polymer is a substrate analog that replaces the native substrate. Furthermore...
Source: Advances in Protein Chemistry and Structural Biology - Category: Biochemistry Source Type: research