Site-Specific PEGylation of Therapeutic Proteins

Abstract

The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG) group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.

Designing Molecular Building Blocks for Functional Polymersomes

“…For example, a bio‐orthogonal functional handle incorporated into a protein can be reacted with a polymer functionalized with a complementary orthogonal handle to form a covalent link between the two ligands. Orthogonal handles include azides, alkynes, aldehydes, aminooxys, and trans‐cyclooctenes . Bertozzi et al .…”

Boronsäuren als bioorthogonale Sonden für zentrenselektives Protein‐Labeling

“…Die Ligationsmethode stellt ein bevorzugtes Mittel zur zentrenspezifischen Modifikation einzelner Seitenketten dar, [1][2][3][4][5] da sie schnell und selektiv verläuft und sogar mit komplexen Proteinmischungen, lebenden Zellen und Organismen kompatibel ist. [28][29][30][31][32] Um diese Anwendungen zu ermçglichen, muss eine ideale bioorthogonale Reaktion einfach und praktisch anwendbar sein Im Laufe der letzten zwanzig Jahre wurden zahlreiche bioorthogonale Reaktionen [4,5,23] entwickelt. [28][29][30][31][32] Um diese Anwendungen zu ermçglichen, muss eine ideale bioorthogonale Reaktion einfach und praktisch anwendbar sein Im Laufe der letzten zwanzig Jahre wurden zahlreiche bioorthogonale Reaktionen [4,5,23] entwickelt.…”

Design and Modification of Anticancer Peptides

“…Among all the kinds of polymers used for the modification of anticancer peptide, PEG was studied most frequently and thoroughly. It has been approved safety by FDA for food, drug delivery vehicle [112][113][114][115]. PEGylated protein and peptide have many advantages, such as the hydrophilic characteristic of PEG moiety enabling to increase the ability of ACPs to escape from degradation of blood serum protein and making the peptides obtained larger molecular weight.…”