Peptides play an important role in drug development and pharmacological research. However, the application of peptides in vivo is limited because peptides can be quickly degraded by proteases, have poor solubility, and are easily filtered by glomeruli in the kidneys. Attaching polyethylene glycol (PEG) to peptides through covalent bonds can reduce the immunogenicity of peptides, increase solubility, and reduce renal clearance, which can effectively solve these problems. Peptide PEGylation is now a widely recognized technology in targeted drug delivery systems. As more and more PEGylated therapeutic drugs are approved by the Food and Drug Administration (FDA), PEG site-specific modification is also gaining more and more attention from researchers. Alfa Chemistry has extensive experience in peptide PEG modification and can perform PEG modification on many sites of peptides.
Our Services
According to the difference in polymerization degree, we can provide low-polymerization degree PEG modification and high-polymerization degree PEG modification services.
- Low-polymerization degree PEG modification. The low-polymerization degree PEG is equivalent to general amino acids or derivatives. After modification to the peptide chain, it can be purified and identified by mass spectrometry normally. The following table shows our commonly used low-polymerization degree PEG modification components.
| Name | Structure |
| m-PEG3-CH2CH2COOH |  |
| NH2-PEG3-CH2CH2COOH |  |
| m-PEG4-CH2CH2COOH |  |
| m-PEG4-NHS |  |
| m-PEG4-Mal |  |
- High-polymerization degree PEG modification. The high-polymerization degree PEG is a mixture. It does not have an accurate molecular weight, but only an average molecular weight, so it cannot be purified by HPLC and identified by mass spectrometry after modification. However, dialysis can be used to remove small molecules in it to achieve the purpose of further purification. The following table shows our commonly used high-polymerization degree PEG modification components.
| Name | Structure |
| m-PEG3-CH2CH2COOH |  |
| NH2-PEG3-CH2CH2COOH |  |
Peptide PEG Modification Methods
The PEG modification of the N-terminal amino group can be directly condensed with a PEG with a carboxyl group. The PEG modification of the C-terminal is relatively complicated, but the PEG derivative with a hydrazide activation group can be used to achieve the PEG modification of the C-terminal carboxyl group of the peptide. In addition, after introducing a thiol group or some specific groups into the preset site of the peptide, and then modifying the group, a site-specific modification product with high activity retention and reduced immunogenicity can also be obtained.
In addition to the peptide PEG modification methods described above, the following three methods are also commonly used for peptide PEG modification:
- Click chemistry. The azide group on PEG is connected to the alkyne group on the peptide through click chemistry.
- Suzuki–Miyaura reaction. The iodine group on PEG and the boronic acid group on the peptide are connected through the Suzuki–Miyaura reaction.
- Sonogashira reaction. The iodine on PEG and the alkyne group on the peptide are connected by the Sonogashira reaction under the catalysis of palladium and copper.
Factors to Consider When Choosing PEG Modification
When choosing PEG modification for a specific application, there are several factors that need to be considered:
- Function. Monofunctional PEG, that is, it contains one chemically reactive end, which can be used for nanomaterial modification. Bifunctional PEG, that is, it contains homologous bifunctional PEG (two reactive ends are the same) or heterologous bifunctional PEG (two reactive ends are different), which is used for conjugation and cross-linking.
- Structure. Linear PEG is usually used for PEGylation and cross-linking in drug delivery systems. Multi-arm PEG (4-arm, 8-arm) can be used to prepare hydrogels and scaffolds for drug delivery.
- Reactivity. PEG with reactive terminal groups, such as -NHS, -SH or -COOH groups, can be covalently conjugated with corresponding functional groups. PEG with acrylate terminal groups can be polymerized by photopolymerization.
- Molecular weight. PEG with higher molecular weight (≥ 5 kDa) is used for conjugation with low molecular weight drugs. PEG with lower molecular weight (≤ 5 kDa) is used for PEGylation of proteins and peptides.
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