Polyethylene Glycol Modification Reagent in Protein Medicine

Modified PEG is also called modified polyethylene glycol, which is a PEG-modified by a chemical modification group or a biologically active group. In drug development and research, in order to increase the half-life of protein or peptide drugs in the body, reduce immunogenicity, and increase the water solubility of drugs at the same time, activated polyethylene glycol is chemically coupled to proteins, peptides, small molecule organic drugs and Liposome. After drugs are modified by PEG, they often have the following advantages:

1)Longer half-life
2)Lower maximum blood concentration
3)Small fluctuations in blood concentration
4)Less enzyme degradation
5)Less immunogenicity and antigenicity
6)Less toxicity
7)Better solubility
8)Reduced medication frequency
9)Improve patient compliance, improve quality of life, and reduce treatment costs
10)Liposomes have a stronger passive targeting effect on tumors

Introduction to the use of modified PEG:

1.PEG modification of protein drug

PEG-modified protein drugs can prolong the half-life of the drug, reduce immunogenicity, and retain its biological activity to the utmost extent. As a therapeutic drug, proteins modified with polyethylene glycol (PEG) are more effective than unmodified proteins. PEG modifies protein drugs mainly including amino modification (including acylation modification of N-terminal amino group, acylation modification of lysine side chain amino group, and alkylation modification of N-terminal amino group), carboxyl group modification, sulfhydryl group modification.
PEG can also modify lumbrokinase, SOD, chymotrypsin, G-CSF, pal enzyme, protein A, protein B, protein cysteine, etc.

2.PEG modification of peptide compounds

PEG modification of peptide compounds, such as PEG modification products of border calcitonin and epidermal growth factor, have a significantly higher half-life and biological activity than prototype drugs. Especially in terms of the site-specific modification of polyethylene glycol, peptide compounds are easier to achieve than proteins. The most common application in the study of PEG modification of peptide compounds is mPEG.

3.PEG-modified liposomes

Liposomes are currently one of the most effective carriers for the transport of various drugs into cells. Common immune liposomes have a short circulating half-life in the blood and are easy to eliminate, which limits their development. PEG-modified long-circulating liposomes can not only escape the capture of the reticuloendothelial system but also improve the passive targeting of liposomes by increasing the blood circulation time of liposomes. It has been widely used in liposome pharmaceutical preparations. The PEG-modified doxorubicin liposome is less cardiotoxic than the original drug, increased patient tolerance, plays the role of controlled release and targeted drugs in the body.

4.PEG-modified organic small molecule drugs

Many small molecule drugs, most of which are anti-tumor drugs. Using PEG modification technology, polyethylene glycol supports small molecules, which can transfer many of its excellent properties to the conjugate. In, the polymer has excellent biocompatibility, can be dissolved in tissue fluid in the body, and can be quickly excreted from the body without any toxic side effects. Many anti-tumor drugs are modified by high molecular weight PEG to achieve passive targeted drug delivery to tumor tissues.PEG The modification method is mainly to couple PEG with the -OH, -NH2, and -COOH on these small molecule drugs. If the small molecule drugs to be modified do not have these functional groups, they can be introduced by chemical methods.

5.Other applications

PEG-modified affinity ligands and cofactors are used in aqueous two-phase distribution systems for purification and analysis of biological macromolecules and cells. PEG-modified carbohydrates can be used as new drug materials and drug carriers. Oligonucleotide PEGylation can increase solubility, increase resistance to nucleases, and cell membrane penetration. PEGylation of biomaterials can reduce thrombus formation and reduce protein and cell adhesion.