PEGylated Peptide Synthesis

PEGylation is a common method to improve peptide stability and bioavailability. Thanks to decades of experience in peptide modification and synthesis, CD Formulation provides a wide range of PEGylation services. Our team has the expertise and knowledge to customize different PEGylation strategies for our customers to meet specific research and application needs.

Advantages of Peptide PEGylation

The covalent attachment of polyethylene glycol (PEG) to a peptide chain is called peptide PEGylation. Due to the enhanced therapeutic properties of PEGylated peptides, improved peptide stability, and bioavailability, this conjugation mechanism may be a solution to overcome many challenges faced by peptide drug candidates.

• Increased Solubility: PEG is hydrophilic and can significantly improve the solubility of peptides in aqueous solutions, making them more suitable for intravenous or other forms of delivery.
• Extended Half-life: PEGylation can prolong the circulation time of peptides in the bloodstream by reducing renal clearance and avoiding rapid degradation by proteolytic enzymes. This extended half-life can lead to less frequent dosing for patients.
• Reduced Immunogenicity: The addition of PEG can mask epitopes on the peptide that might elicit an immune response, reducing the likelihood of immunogenic reactions.
• Improved Stability: PEGylation can enhance the chemical and enzymatic stability of peptides, protecting them from degradation in biological environments and extending their shelf life.
• Enhanced Bioavailability: By improving solubility and stability, PEGylation can enhance the bioavailability of administered peptides, leading to better therapeutic outcomes.
• Targeted Delivery: PEGylated peptides can be designed to target specific tissues or cells, improving localized treatment and minimizing systemic exposure.

Fig. 1 Schematic diagram of PEG–peptide conjugates. (Hamley IW, et al., 2014)

Explore Our Custom PEGylated Peptide Synthesis Services

As experts in peptide modification, CD Formulation provides unparalleled peptide PEGylation services to clients around the world. We have reliable synthesis procedures and superior peptide analysis technologies to address any possible challenges in the development and production of peptide therapeutics.

Our team of peptide modification experts can perform site-specific PEGylation at different sites of the peptide, including:

N-Terminal PEGylation

This modification is achieved by direct polyethylene glycol carboxylic acid coupling or chemical connection of polyethylene glycol thioesters to cysteine residues.

C-Terminal PEGylation

C-terminal PEGylation is a more complex process, mainly achieved by thiocarboxylic acid modification and sulfonyl-azide PEG reagents. In addition, hydrazide combined with acetone acylating reagents is another C-terminal PEGylation method.

Other PEGylation

In addition to the N-terminus and C-terminus, amino acid chains with appropriate functional groups can be PEGylated.

Our Synthesis Methods for PEGylated Peptide

PEG and peptides are usually conjugated via amide bond formation, but other linkage chemistries are possible, such as thiol-maleimide, oxime linkage, and click chemistry. To ensure site-specific PEGylation, we typically use the following 3 methods:

Click Chemistry

This reaction occurs between the azide group of the PEG reagent and the alkyne group of the peptide (such as Huisgen 1,3-coupling reaction), which can achieve highly selective and efficient PEGylation. This method can ensure the connection of PEG to the peptide at a specific site.

Amide Bond Connection

Specific amino acid residues such as lysine, aspartic acid, etc., are used to connect polyethylene glycol (PEG) to peptides. Site-specific connection is achieved by introducing functionalized amino acids at specific sites of the peptide chain.

Bioorthogonal Reactions

Bioorthogonal chemical reactions, such as thiol-maleimide reaction and oxime reaction, are used to selectively carry out PEG modification on specific amino acids. These reactions usually don't occur under in vivo conditions and therefore have better biocompatibility.

Available PEG Options

PEG and its derivatives are nonionic, nontoxic, biocompatible, and highly hydrophilic polymers that have been widely used in custom peptide synthesis to improve the solubility of hydrophobic peptides, increase the bioavailability of bioactive peptides, and protect peptides from eliciting immune responses. Regulatory approvals have been granted for PEGylated drugs with varying PEG chain lengths, ranging in molecular weight from 5 -40 kDa.

PEGs are mainly classified into two categories:

• Polydisperse PEG: Long chains consisting of more than 60 atoms and a mixture of oligomers of different sizes with a broadly or narrowly defined molecular weight (MW) range.
• Monodisperse PEG: Short chains with a precisely defined number of PEG units and a defined molecular weight, often used as linkers or spacers. Bifunctional PEGs are common linkers and spacers for peptide conjugation and labeling. These PEG derivatives can be applied in SPPS and LPPS.

m-PEG2-amine	azido-PEG2-amine	propargyl-PEG2-amine
amino-PEG2-amine	amino-PEG2-acid	PEG8
biotin-PEG2-amine	mini-PEG3	Custom PEGs

Peptide Manufacturing & Analytical Services

In addition to peptide synthesis capabilities, CD Formulation combines flexible GMP manufacturing facilities with cutting-edge peptide analytical knowledge to provide a full range of quality control testing services to accelerate the commercialization of your products, including:

Publication

CD Formulation has extensive experience with each PEGylation peptide modification. Please don't hesitate to contact us if you are interested in our services, and to learn more about the possibilities of incorporating PEG into your peptides. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.