Chemistry for peptide and protein PEGylation

Intravenous Administration of Polyethylene Glycol-Coated (PEGylated) Proteins and PEGylated Adenovirus Elicits an Anti-PEG Immunoglobulin M Response

“…[1][2][3] PEG is one of the most versatile synthetic polymers and is widely believed to lack immunogenicity and toxicity and shows high solubility in water and in many organic solvents. 4,5) For instance, proteins modified with PEG have an increased solubility due to the hydrophilicity of grafted PEG; their destruction by protease and the immune system is decreased due to the steric hindrance of grafted PEG; and, glomerular filtration is decreased due to an increase in the apparent size or hydrodynamic volume of a given protein. [6][7][8] Consequently, the pharmacokinetics of bioactive proteins is improved and thereby the PEGylated proteins become useful for therapy.…”

“…However, their application is sometimes limited due to their insufficient clinical effects as a result of susceptibility to destruction by proteolytic or nucleolytic enzymes, a short circulating half-life, low solubility, rapid kidney clearance and propensity to generate neutralizing antibodies. 4) Covalent conjugation of polyethylene glycol (PEG) to the biological active molecules, by a process called "PEGylation," is one of the promising strategies being used to overcome these limitations. [1][2][3] PEG is one of the most versatile synthetic polymers and is widely believed to lack immunogenicity and toxicity and shows high solubility in water and in many organic solvents.…”

Preparation of monoPEGylated Cyanovirin-N’s derivative and its anti-influenza A virus bioactivity in vitro and in vivo

“…Three proteins inhibited the propagation of influenza virus in chicken embryos by haemagglutination assay (X ± s). CVN derivative and it's anti-IAV bioactivity attaching PEG chains to polypeptides or other lead molecules (13,14). This technique has become the leading approach for overcoming most of the aforementioned limits of the biologics.…”

Mu-Opioid Receptor Antagonists and Their Role in Treatment of Chronic Constipation

“…The PEGylation of the 6-α-hydroxyl side chain of naloxone confers increased oral bioavailability and peripheral selectivity to the naloxone moiety by a reduction in passive permeability across the blood-brain barrier [35]. It is also a substrate of the P-glycoprotein (PGP) transporter, which promotes efflux of naloxegol and serves to further restrict its entry into the central nervous system, [36] thus not affecting the analgesic mechanism of opioids in the central nervous system.…”