AUTHOR=Belén Lisandra Herrera , Rangel-Yagui Carlota de Oliveira , Beltrán Lissabet Jorge F. , Effer Brian , Lee-Estevez Manuel , Pessoa Adalberto , Castillo Rodrigo L. , Farías Jorge G. TITLE=From Synthesis to Characterization of Site-Selective PEGylated Proteins JOURNAL=Frontiers in Pharmacology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01450 DOI=10.3389/fphar.2019.01450 ISSN=1663-9812 ABSTRACT=

Covalent attachment of therapeutic proteins to polyethylene glycol (PEG) is widely used for the improvement of its pharmacokinetic and pharmacological properties, as well as the reduction in reactogenicity and related side effects. This technique named PEGylation has been successfully employed in several approved drugs to treat various diseases, even cancer. Some methods have been developed to obtain PEGylated proteins, both in multiple protein sites or in a selected amino acid residue. This review focuses mainly on traditional and novel examples of chemical and enzymatic methods for site-selective PEGylation, emphasizing in N-terminal PEGylation, that make it possible to obtain products with a high degree of homogeneity and preserve bioactivity. In addition, the main assay methods that can be applied for the characterization of PEGylated molecules in complex biological samples are also summarized in this paper.