Polyethylene glycol (PEG) is a safe, inactive, and nontoxic polymer that is commonly used for molecular modification. Therapeutic benefits of protein modification with polyethylene glycol include reduced renal and cellular clearance and increased half-life; enhanced protection against proteolysis; and reduced toxicity. The purpose of PEGylation of biologically active proteins is to improve their pharmacokinetic and pharmacodynamic properties while retaining the intrinsic biological activity of the native protein. In order to improve the pharmacological activity and clinical efficacy, the pharmacokinetics and pharmacodynamics of polyethylene glycol proteins need to be optimized, and the structure, length, molecular weight and modification methods of the PEG polymer chain are all factors that affect the optimization.
Polyethylene glycol modification, also known as PEGylation of molecules, is a modification method developed in the late 1970s. Coupling of activated polyethylene glycol with protein molecules affects the spatial structure of the protein, ultimately leading to changes in various biochemical properties of the protein: increased chemical stability, improved resistance to proteolytic hydrolysis, reduced immunogenicity and toxicity or disappear, the half-life in vivo is prolonged, and the plasma clearance rate is reduced.
Polyethylene glycol molecules contain a large number of ethoxy groups, which can form hydrogen bonds with water, so they have good water solubility and are soluble in most organic solvents except ether, hexane, and ethylene glycol. After most proteins are modified with polyethylene glycol, in addition to retaining or increasing their water solubility, they can also obtain solubility in some organic solvents. In protein solution, polyethylene glycol, whether in free or bound form, has no adverse effects on protein molecules even at high concentrations. The general conformation of polyethylene glycol-modified proteins does not change, and the biological activity of the conjugates is mainly produced by the protein part of the conjugates.
In recent years, biological macromolecular drugs such as protein peptides and natural product drug molecules have been increasingly used in the field of disease treatment, which has greatly promoted the development of the pharmaceutical industry. However, the role of biological macromolecules in the medicinal process is greatly limited due to their short half-life, easy to produce immunogenic antigenicity, easy enzymatic hydrolysis, and certain pharmacological toxicity. In order to effectively solve this problem, the purpose of prolonging the drug effect is achieved by chemically modifying the drug molecule with polyethylene glycol. Because of the steric hindrance of the polyethylene glycol chain, the resistance of the modified protein to protease hydrolysis is greatly improved, and the molecular exclusion volume of the modified molecule is significantly increased, so that the renal filtration clearance rate is significantly reduced. At the same time, the structural specificity of the polyethylene glycol molecule reduces the ability of the liver reticuloendothelial system to recognize, uptake and clear the modified protein, and can reduce or eliminate the ability to induce neutralizing antibodies and bind to antibodies, making it It is difficult to be recognized and cleared by the immune system. These effects make the polyethylene glycol-modified drug molecules have better pharmacological and pharmacokinetic properties than unmodified drugs.
Polyethylene Glycol (PEG) linkers usually have better aqueous solubility and lower immunogenicity. they are widely used in ADC bioconjugation research. PEG linker provides the research community a powerful tool to improve the physio-chemical property of the bioconjugation complex.
AxisPharm has over 5,000 high purity PEG reagents kept in stock. The wide selection of lengths and functionalities will empower the PEGylation, bioconjugation, crosslinking, ADC drug development, and biolabeling for pharmaceutical and biotech R&D.
AxisPharm offers a range of PEG based reagents with different linker lengths, bearing various reactive groups. such as mPEG, PEG Acid, PEG Amine, PEG Azide, Maleimide PEG, NHS ester PEG, Bromide PEG and others.You can learn more by the following categories.