Pegylation

Pegylation is a process that involves the covalent and non-covalent attachment of polyethylene glycol (PEG) polymer chains to molecules and macrostructures, such as a drug or therapeutic protein, which allows for improved functionality of the molecule. This process is used in the field of drug delivery for the purpose of improving the safety and efficiency of therapeutic agents.

History

The concept of Pegylation was first introduced in the 1970s by Abuchowski and colleagues, who attached PEG to bovine serum albumin (BSA) and liver catalase in order to increase their circulating half-lives.

Process

Pegylation involves the attachment of PEG to the molecule of interest via a covalent bond. This is typically achieved through the use of a PEG derivative that has been functionalized with a reactive group, such as a carboxylic acid or amine. The reactive group on the PEG derivative can then form a covalent bond with a complementary reactive group on the molecule of interest.

Benefits

Pegylation can significantly improve the pharmacokinetics of a drug or therapeutic protein. The attachment of PEG to a molecule can increase its size, which can reduce renal clearance and prolong the circulating half-life of the molecule. Pegylation can also increase the solubility of a molecule, which can improve its bioavailability. Furthermore, Pegylation can reduce the immunogenicity of a molecule, which can reduce the risk of adverse immune reactions.

Applications

Pegylation has been used to improve the properties of a variety of therapeutic agents, including proteins, peptides, antibodies, oligonucleotides, and small molecule drugs. Examples of Pegylated drugs that have been approved for clinical use include Pegasys (Pegylated interferon alpha-2a) for the treatment of hepatitis C, and Neulasta (Pegylated granulocyte colony-stimulating factor) for the prevention of neutropenia in cancer patients.

See also

• Drug delivery
• Pharmacokinetics
• Polyethylene glycol
• Protein engineering