Custom Synthesis PEG Derivatives

BOC Sciences provides many types of activated PEGs with wide variety of functional groups, whereby can be further introduced into small molecule drugs, enzymes, peptide and proteins, nanoparticles and other biologics, playing important roles in the augmentation the targeting ability, stabilization of conjugates, reduction of their antigenicity and/or decrease in the drug doses.

What are Polyethylene Glycols?

Polyethylene glycol (PEG) has a variety of attractive structural, physical, and biophysical properties, including a stable, flexible, and neutral backbone, and good solubility in water and many other solvents. It is biocompatible, non-immunogenic and non-antigenic. Therefore, PEGylation of biological macromolecules to improve drug solubility and stability, reduce immunogenicity and frequency of administration has been widely used in the pharmaceutical industry and biomedical research. PEG used for such applications requires a size of 4K Da to have the desired biophysical effect, with the most commonly used size being 40K Da. In addition to its use as PEGylating agents in pharmaceuticals, PEG and its derivatives are frequently used in other fields, including surface science, nanotechnology, carbon nanotube functionalization, organic-inorganic hybrid materials, and bioconjugation. In some of these cases, the size may be less than 1K Da, and these compounds are more appropriately called oligoethylene glycols (OEGs).

Fig. 1. Synthesis and applications of polyethylene glycol (Expert opinion on drug delivery, 2009, 6(1): 1-16).

PEG Synthesis

The synthesis of PEG involves the polymerization of ethylene oxide, a simple and widely used monomer. PEG obtained by polymerization of ethylene oxide has one or two terminal hydroxyl groups (mPEG-OH or HO-PEG-OH), depending on the polymerization initiator: methanol or water, respectively. Since the repeating ethylene oxide units of PEG do not have reactive side groups, PEG is combined with other compounds through terminal functional groups to achieve activation. The polymerization of ethylene oxide to form PEG can be carried out by a variety of methods, including anionic polymerization, cationic polymerization and coordination polymerization. Anionic polymerization is the most common method for the synthesis of PEG because it allows precise control of the molecular weight and end-group functionality of the polymer. In addition, polydispersity index (PDI) is a parameter describing the uniformity of molecular weight distribution of PEG. The closer the PDI value is to 1.0, the more uniform the size distribution of the PEG molecules, that is, the lower the dispersion of the polymer; while the PDI value greater than 1.1 usually indicates that the polymer has a wider molecular weight distribution, that is, the polymer has higher dispersion.

At BOC Sciences, we have a team of experienced chemists and scientists specializing in the synthesis of PEG molecules with precise molecular weight, chain length, and end groups. Our state-of-the-art facilities and advanced equipment allow us to perform PEG synthesis from milligram to kilogram scales, ensuring we can meet the needs of our customers, whether they require small quantities for research purposes or large quantities for commercial production. Our PEG synthesis technology supports:

Anionic Polymerization of PEG

In anionic polymerization, an initiator such as an alkali metal alkoxide or metal hydride is used to initiate the polymerization of ethylene oxide. The initiator reacts with the ethylene oxide monomer to form an alkoxide ion, which then attacks another ethylene oxide molecule to form a growing polymer chain. This process is repeated until the desired molecular weight is reached. The end-group functionality of the polymer can be controlled by using different initiators or by adding functional monomers during the polymerization process. The process of synthesizing PEG through anionic ring-opening polymerization is as follows:

Step 1: The PEG initiator (usually a monomeric PEG molecule) reacts with a catalyst (usually potassium hydroxide). In this process, the PEG initiator is activated and generates alkoxide ions.

Step 2: Reaction of activated PEG with ethylene oxide (EO). During this process, alkoxide ions perform a nucleophilic attack on the epoxide ring, forming a new ether bond. This process is repeated multiple times to form polymer chains.

Step 3: Terminate the aggregation process. A quenching agent, such as acetic acid, is added during this process to deactivate the catalyst and prevent further polymerization.

Stepwise Organic Synthesis of PEG

Currently, the longest PEG that can be synthesized using stepwise organic synthesis is a PEG with approximately 45 ethylene glycol units, which corresponds to a molecular weight of approximately 2K Da. There are several different routes for stepwise organic synthesis of PEG, including unidirectional iterative coupling, bidirectional iterative coupling, chain multiplication, and chain triplication. The process involves several steps including ethylene oxide production, polymerization, purification, functionalization, characterization and packaging. Each step is carefully controlled to ensure the production of high-quality PEG with the properties required for a variety of applications. PEG's versatility and biocompatibility make it an ideal polymer for a wide range of uses, and its synthesis process is continuously optimized to improve efficiency and quality.

Solid Phase Synthesis of PEG

Solid-phase technology is a method of synthesizing compounds on a solid support rather than in solution. In PEG synthesis, solid-phase techniques can control the growth of polymer chains on a solid support, resulting in a high degree of purity and homogeneity in the final product. The synthesis of PEG via solid-phase techniques typically involves the use of a resin-based solid support to which the first monomer unit is attached. The monomer units then react with linker molecules, which act as bridges between the solid support and the growing polymer chain. Subsequent monomer units are added one at a time, each addition requiring activation of the monomer and removal of any protecting groups. Repeat this process until the desired chain length is reached. One of the key advantages of solid-phase techniques for PEG synthesis is the ability to control polymer chain length and composition with high precision. Furthermore, the use of solid supports allows for easy purification of the final product, as any impurities can be removed with simple washing steps.

PEG Derivatives We Can Offer

PEGylation Services

One of the key advantages of our PEG synthesis services is our ability to tailor the properties of PEG molecules to meet our customers' specific requirements. We offer a variety of PEG derivatives, including monofunctional and multifunctional PEGs, PEG diols, PEG amines, PEG acids, and PEG methacrylates, among others. These derivatives can be further modified with various functional groups (e.g., carboxylic acids, amines, alcohols, and thiols) to impart specific properties to the PEG molecules, such as increased stability, solubility, or reactivity.

In addition to customizing the properties of PEG molecules, we offer a variety of PEGylation services, which involve covalently linking PEG chains to biomolecules such as proteins, peptides, antibodies, and nucleic acids. Our PEGylation services include site-specific PEGylation, where a PEG chain is attached to a specific amino acid or functional group on a biomolecule, as well as random PEGylation, where a PEG chain is attached to multiple sites on a biomolecule. point). We also offer a range of PEG linkers for conjugating PEG chains to biomolecules via a variety of chemical reactions such as thiol-maleimide, amine-NHS, and alkyne-azide click chemistry.

Why Choose BOC Sciences?

• Rich R&D experience, can provide super multi-functional group modification options
• Good performance, high purity, product polymerization dispersion degree (PDI) less than 1.05
• Wide distribution range of molecular weight, 200-400,000 can be satisfied
• Simplified production process, low impurities, stable quality
• Mass production, short turnaround time, controllable costs
• Multi-batch test experience supports rapid completion of routine reaction types
• Customers' special customization needs can be completed within a short period of time
• Rigorous quality standards from raw material sourcing and synthesis to purification and characterization
• Advanced analytical techniques include NMR, HPLC, MALDI-TOF mass spectrometry, and more

How to Order?

Reference

1. Bento, C. et al. Striving for uniformity: a review on advances and challenges to achieve uniform polyethylene glycol. Organic Process Research & Development.