abstract
The covalent attachment of polyethylene glycol (PEG) to therapeutical proteins is an important route to develop biobetters for biomedical, biotech and pharmaceutical industries. PEG conjugation can shield antigenic epitopes of the protein, reduce degradation by proteolytic enzymes, enhance long-term stability and maintain or even improve pharmacokinetic and pharmacodynamics characteristics of the protein drug. Nonetheless, correct information in terms of the PEGylation process from reaction to downstream processing is of paramount importance for the industrial application and processing scale-up. In this review we present and discuss the main steps in protein PEGylation, namely: PEGylation reaction, separation of the products and final characterization of structure and activity of the resulting species. These steps are not trivial tasks, reason why bioprocessing operations based on PEGylated proteins relies on the use of analytical tools according to the specific pharmaceutical conjugate that is being developed. Therefore, the appropriate selection of the technical and analytical methods may ensure success in implementing a feasible industrial process.
keywords
SITE-SPECIFIC PEGYLATION; CAPILLARY ELECTROPHORETIC SEPARATION; MASS-SPECTROMETRIC ANALYSIS; AQUEOUS 2-PHASE SYSTEMS; MOLECULAR-WEIGHT; IMMUNOLOGICAL-PROPERTIES; POLY(ETHYLENE GLYCOL); ALPHA-LACTALBUMIN; SERUM-ALBUMIN; CYTOCHROME-C
subject category
Pharmacology & Pharmacy
authors
Santos, JHPM; Torres-Obreque, KM; Meneguetti, GP; Amaro, BP; Rangel-Yagui, CO
our authors
João Henrique Picado Madalena Santos
PhD Studentacknowledgements
The authors acknowledge the National Council for Scientific and Technological Development (CNPq - Brazil), the Coordination for the Improvement of Higher Education Personnel (CAPES-Brazil), the Sao Paulo Research Foundation (FAPESP - Brazil, grant #2016/22065-5) and the Portuguese Foundation for Science and Technology (FCT) for the doctoral grant SFRH/BD/102915/2014 to J. H. P. M. Santos. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement.