PEG Linkers And Their Applications In Different Fields

Numerous applications of PEGs have been reported in the scientific literature over the years. Due to their solubility in water, excellent biocompatibility and non-immunogenicity, PEG linkers are widely used in biological and medical research, such as antibody-drug conjugates, nanoparticle drug delivery, biotinylation, PEGylation protein drugs and small molecule drugs, etc.

What are PEG Linkers?

PEG linkers, also known as PEG reagents, are chemically functionalized PEG linkers. PEG linkers are particularly attractive as a cross-linker for conjugation and biolabeling, due to their water solubility, lack of toxicity, low immunogenicity.

Monodispersed and polydispersed are two classes of PEG linkers. Monodispersed PEG has an exact number of PEG units with a specific single chemical structure with precise molecular weight. But the molecular weight of polydisperse PEG is indeterminate and distributed within a certain range.

Application of PEG Linkers

Long-acting drugs are the traditional application of PEGylation. They have been clinically used for more than 30 years and have gradually become the mainstream solution for long-acting drugs. With the deepening of PEGylation research, its application fields have been continuously expanded. In addition to polypeptide and protein drugs, it is also used in small molecule drugs, ADC drug linkers, gene drug (siRNA, mRNA) delivery and hydrogel-based devices, etc.

1. PEG Linkers in Long-Acting Drugs (Mainly Protein & Peptide Drugs)

In the 1970s, Professor Frank Davis of Rutgers University modified bovine serum albumin with PEG to reduce the immunogenicity of recombinant proteins, prolong their metabolism in vivo, and enhance protein activity. Since then, the technology has been widely used in many fields of biomedicine. In 1990, the FDA approved Adagen® (pegademase bovine), the world's first PEGylated drug for the treatment of severe combined immunodeficiency disease. Since then, PEGylated ADA, IFN, CPT, rhG-CSF, L-asparaginase, and many other products have been introduced. Up to now, there are more than 30 FDA- or EU-approved PEGylated drugs on the global market, with a market size of over $10 billion.

2. PEG Linkers in Small Molecule Drugs

PEGylation can address certain deficiencies in the physicochemical properties and pharmacokinetics of small molecule drugs.

First, the problem of water solubility of drugs can be solved.  

Secondly, the half-life of the drug can be increased.

In addition, PEGylation has a significant toxicity-reducing effect on antitumor small molecule drugs.

3. PEG Linkers in Drug Delivery

PEGylated drug delivery platforms are the frontier application area of PEG in the pharmaceutical field. PEGylation technology can also be applied to delivery systems such as siRNA, mRNA, and pDNA. The development of related technologies in the future will significantly promote the development of PEGylated drug delivery platforms. LNP (Lipid Nanoparticle) is the most mainstream non-viral vector for the delivery of mRNA to target cells.

4. PEG Linkers in Antibody Drug Conjugate (PEG8/12)

ADC (antibody-drug conjugate) drugs are composed of monoclonal antibodies, linkers and active drugs. A suitable linker helps maintain the stability between the antibody and the drug and helps the antibody to selectively deliver the drug to tumor cells and accurately release the drug.

PEG is one of the most widely used linkers in targeted therapy. Two of the latest ADCs to be approved, Trodelvy and Zynlonta, were developed with PEG moiety as part of their linker technology to improve solubility and stability in vivo.

As a reliable PEG products supplier, Biopharma PEG can provide high purity PEG linkers for your biological and medical research, from lab scale to GMP commercial scale.