Peptide PEGylation

Creative Peptides is pleased to offer a continuously growing and diverse portfolio of PEGs that will help you improve the success of your drug discovery studies. For PEGylated peptides, PEG is typically attached to the peptide via standard amide bond formation, but other bonding chemistries (e.g., mercapto-maleimide, oxime linkage, click chemistry) can also be used. Creative Peptides has extensive experience with these PEG coupling chemistries to overcome many of the challenges of peptide drug candidates.

PEGylation of Peptides

PEGylation is the process of covalently attaching polyethylene glycol (PEG) chains to peptides, proteins, or other biomolecules. PEGs are non-ionic, non-toxic, biocompatible and highly hydrophilic polymers. PEGylation of peptides can enhance therapeutic properties due to their increased solubility (for hydrophobic peptides), prolonged half-life by reducing renal clearance, and masking of antigenicity to reduce host immune response.

Fig. 1. Structure of PEGylated polyacridine peptides (Gene therapy. 2020, 27(5): 196-208).

Services for PEGylated Peptides

Creative Peptides provides high-quality peptide modification services, including biotinylation, PEGylation, etc., which can lead to a variety of developmental possibilities for our clients' projects.

• Design of PEGylated Peptides

Factors to be considered in the design of PEGylated peptides include: the length of the PEG chain, the site of PEG modification, the linkage of the PEG to the peptide, and the control of the density of the PEG modification. In addition, several factors need to be considered comprehensively, including the characteristics of the peptide, the application requirements and the feasibility of the synthesis method.

• Preparation of PEGylated Peptides

Creative Peptides' technicians perform PEG activation followed by binding with custom synthesized peptides to complete the peptide modification. The method of preparation can be divided into terminal PEGylation and side chain PEGylation. After completing the peptide preparation, the product needs to be purified, and the purification methods include dialysis, gel filtration and reverse phase high-performance liquid chromatography. In addition, we also provide validation services for PEGylated peptides, including mass spectrometry and nuclear magnetic resonance.

• Development of PEGylated Peptides

In addition to simple PEG modifications, Creative Peptides can introduce other functional groups onto PEG chains or peptide molecules to achieve multifunctionalized designs. For example, the introduction of functional groups such as targeting ligands, fluorescent markers, radioisotopes, etc. enables the PEGylated peptide to have various functions such as targeted delivery, imaging and therapeutic monitoring.

Available PEGylated Peptides

• PEG Carrier

• PEG Spacer

• Mini-PEG1

• Mini-PEG2

• Mini-PEG3

Applications of PEGylated Peptides

Enhancing drug stability and circulation time. PEG modification can slow down the rate of peptide degradation by enzymes, thus prolonging its residence time in the body and improving the efficacy of the drug.

Reducing immunogenicity and increase tolerance. PEG can mask the immunogenic sites on peptide molecules, reducing the recognition and immune response of the immune system to the peptide. This helps reduce the side effects of peptide drugs and increases their tolerability in patients.

Improving drug delivery properties. PEG modification increases the permeability and penetration of peptides across cell membranes, which improves drug absorption and distribution in the body. This has important application potential for oral absorption, tissue-targeted delivery and blood-brain barrier permeation of peptide drugs.

Improving water solubility and stability of drugs. PEGylation can improve the water solubility of peptide drugs and increase their stability in aqueous solution.

Advantages of PEGylated Peptides

• Cost-effective custom synthesis services
• Synthesis of monodisperse functionalized PEG derivatives
• In quantities of several milligrams up to 100 grams
• Quality assurance: HPLC chromatogram and mass spec analysis
• Highly skilled and committed scientific staff

References

1. Mathew, B. et al. Heat-shrinking DNA nanoparticles for in vivo gene delivery. Gene therapy. 2020, 27(5): 196-208.
2. Harris, J.M. et al. Pegylation. Clinical pharmacokinetics. 2001, 40(7): 539-551.
3. Veronese, F.M. et al. Peptide and protein PEGylation: a review of problems and solutions. Biomaterials. 2001, 22(5): 405-417.
4. Veronese, F.M. et al. PEGylation, successful approach to drug delivery. Drug discovery today. 2005, 10(21): 1451-1458.