The Effect Of PEG Modification On Proteins



1. Increase solubility and stability

Pharmaceutical PEG is easily soluble in water and most polar solvents, but insoluble in non-polar solvents such as aliphatic hydrocarbons, benzene and mineral oil. As the relative molecular weight increases, the solubility in acute solvents decreases gradually. Since PEG is covalently attached to proteins such as macromolecules, its natural conformation produces a certain rigidity, which is not easy to stretch and inactivate, which reduces the thermal shock of groups within the molecule, thereby increasing thermal stability.

2. Reduce immunogenicity and antigenicity, reduce toxicity and side effects

The effect of eliminating or reducing the antigenicity of macromolecules such as proteins is obvious. L-asparaginase can be modified with PEG to eliminate antigenicity.

3. Extend plasma half-life and increase systemic exposure in vivo

After many proteins and other macromolecules are modified by PEG, the ability to resist proteolytic enzymes, inhibitors and other inactivating factors and thermal stability are improved, and their half-life in vivo is longer than that of natural proteins and other macromolecules. The effect is very meaningful. The in vivo half-life of L-asparaginase can be extended by 13 times after PEG modification.

Some proteins and other macromolecules can be modified by PEG to change the distribution ability of tissues and can be selectively absorbed by target organs in the blood.

4. Increase in vivo biological activity and efficacy

Some PEG-modified proteins and other macromolecules have improved resistance to proteolytic enzyme hydrolysis, inhibitors, acid-base and organic solvents and other denaturation inactivation. The reason is that the steric shielding created by PEG blocks the attack of inactivating factors. In addition, groups sensitive to inactivating factors such as proteolytic enzymes in macromolecules such as proteins are modified to improve their ability. The anti-trypsin and chymotrypsin hydrolysis ability of catalase was significantly improved after PEG modification.

5. Reduce the number of administrations and reduce the pain of patients

PEG can reduce the toxicity of most proteins and other macromolecules, and is non-toxic (relative molecular mass>1 000). PEG with a relative molecular mass of 4000 can be safely injected in a 10% solution at a dose of 16g ​​per kilogram of body weight. In mice, rabbits, monkeys and other animals, it does not harm proteins and cells.