PEGylation is the process of attachment between polyethylene glycol polymer chains and molecules such as drugs, therapeutic proteins or vesicles. Covalent attachment of PEG to a drug or therapeutic protein can protect the drug from the host immune system and prolong its circulatory time by reducing renal clearance. PEGylation can also increase water solubility of hydrophobic drugs and proteins. PEGylation has been widely used in pharmaceutical and biotechnology applications such as protein and peptide PEGylation, ADC conjugation, drug delivery and surface modification.
Figure 1. The reaction of cyanuric chloride activated PEG with the primary amine groups of bovine serum albumin
Alfa Chemistry offers a variety of PEG linkers that improve drug solubility and stability, and discover new drug delivery formats.
PEGylation is the process of attaching a polymer PEG chain to a molecule, most typically peptide, protein, and antibody fragment, which can improve the safety and efficiency of many therapeutic agents. It can produce changes in physicochemical properties, including conformational changes, electrostatic binding, and hydrophobicity, which increases the systemic retention of therapeutic agents. Moreover, it can affect the binding affinity of the therapeutic moiety to the cellular receptor and alter the pattern of absorption and distribution.
PEGylation can impart several pharmacological advantages, such as improving drug solubility, reducing dosing frequency, potentially reducing toxicity, increasing drug stability and enhancing protection against proteolytic degradation.
Figure 2. The introduction of PEG aldehyde derivatives in N-alkyl conjugation
Medicinal use: The clinical value of PEGylation is well established. ADAGEN (pegademase bovine) is the first marketed PEGylated protein approved by the U.S. Food and Drug Administration (FDA). As an alternative to bone marrow transplantation, it is used to treat severe combined immunogenic syndrome (ADA-SCID). Since the introduction of ADAGEN, a large number of PEGylated proteins and peptides have been used, and many other drugs are in clinical trials or under development. Examples of PEGylated drugs currently on the market are: Adynovate is a PEGylated antihemophilic factor VIII for the treatment of hemophilia A; Pegaptanib is used for the treatment of neovascular age-related macular degeneration.