PEG linkers have been widely used in drug discovery, ADC development, bioconjugation and labeling, nanoparticle drug delivery, and polyethylene glycol. PEG linkers are chemically functionalized polyethylene glycol (PEG) linkers. Due to their water solubility and non-immunogenicity, PEG linkers are particularly attractive as very powerful tools in the scientific community for conjugation, drug discovery, nanoparticle drug delivery, chemical biology, and biomarkers.
There are two classes of PEG, monodisperse and polydisperse. Monodisperse PEG linkers have precise numbers of PEG units with specific chemical structures and precise molecular weights. Whereas, polydisperse PEG (also known as polymeric PEG or PolyPEG) is a polymer with an average molecular weight.
Examples of PEG applications
PEG in Antibody Drug Conjugates: In Antibody Drug Conjugates (ADCs), the linker between the antibody and the payload can significantly affect the potency, stability, selectivity, and DMPK of the antibody drug conjugate. For example, the ADC drug Zynlonta incorporates several interesting linker components, including maleimide PEG8 and an enzymatically cleavable linker (Val-Ala), to attach the payload to the antibody.
PEG in Nanoparticle Drug Delivery: With the development of Moderna and Pfizer’s COVID-19 vaccine, lipid nanoparticle drug delivery has now made a name for itself. Typically, delivery systems consist of high transition temperature phospholipids, PEG lipids, and ionizable cationic phospholipids. A specific example is DSPE-mPEG 2000, which is critical to the production of Pfizer’s COVID-19 vaccine. Another well-known pegylated lipid is DMG-PEG 2000, which is used in Moderna’s COVID-19 vaccine.
PEG in Small Molecule Drugs: The introduction of a PEG linker into a small molecule drug increases the solubility and molecular weight of the drug. It allows to prolong the half-life of the drug in the body. Naloxegol (Movantik) is an example of a small molecule drug that incorporates PEG to increase the efficiency of the drug by reducing its transport across the blood-brain barrier.