PEG & PROTAC Solutions

PROTACs (proteolysis targeting chimeras) are heterobifunctional molecules composed of two ligands. The PROTAC molecule consists of three parts: a ligand that binds to the target protein, a ligand that recruits E3 ubiquitin ligase, and a linker between the two. Targeted protein degradation induced by PROTACs has become a novel therapeutic strategy in drug development, favored by academic institutions, large pharmaceutical companies, and biotechnology companies. As a leading manufacturer of PEG derivatives, BOC Sciences is fully capable of providing high-purity PEG products for PROTAC research companies. With a comprehensive and advanced platform, the company provides PEG derivatives and related products to global customers to meet new drug delivery goals.

What are PROTACs?

The PROTAC molecule forms a stable ternary complex with the target protein and E3 ubiquitin ligase. The E3 ubiquitin ligase labels the target protein with ubiquitin, and the ubiquitinated target protein is recognized and degraded by the proteasome. The non-covalent PROTAC molecules can dissociate from the ternary complex and reused. The enzyme ligands and target protein ligands are connected by linkers. Therefore, the design and selection of linkers are very important for the druggability of PROTAC molecules. The type, length and connection site of the linker will affect the structural rigidity, hydrophobicity and solubility of the PROTAC, thereby affecting the formation of the complex and the final degradation activity. The optimal length of PROTAC linkers has been reported to vary from 12 carbons to more than 20 carbons. Linkers commonly used in PROTAC development are PEG, alkyl chains, and alkyl/ether. Among them, 54% of the reported PROTAC molecules used PEG as a linker.

Fig. 1. Mode of action of PROTACs (Sig Transduct Target Ther 4. 2019, 64).

Advantages of PEG Linkers

Compared with general small molecule inhibitors, PROTAC molecules exhibit excellent high selectivity, low toxicity, and can effectively overcome the drug resistance of traditional small molecule inhibitors. PEG linker usually has the following advantages in PROTAC:

• The introduction of PEG can increase the water solubility of PROTAC molecules, thereby affecting cell permeability and oral absorption rate.
• Systematic changes in linker length can be easily achieved by using PEGs of different chain lengths, thereby affecting the degradation efficiency of PROTAC molecules.
• The use of various bifunctional PEG linkers enables simple and rapid assembly of molecules with different linking groups, and accelerates the screening to obtain effective degradation structures.

Our PEG CDMO Capabilities

BOC Sciences provides CDMO services for PEG and lipid manufacturing up to the Megaton (Mt) scale. Our ISO 9001 and ISO 13485 certified facilities strictly follow the ICH Q7A guidelines, enabling the delivery of GMP-grade PEG and lipid derivatives for applications within pharmaceuticals and pioneering technologies. In addition to advanced analytical instruments that support quality control and assurance, we also employ HPLC utilizing various detectors (CAD, UV, ELSD) for purity determination, NMR for structural confirmation, GFC/GPC for size-based analysis, MALDI Spectrometry for mass analysis, etc.

Our PEG Solutions for PROTACs

BOC Sciences focuses on providing high-quality PEG linkers with various active groups, and continues to assist customers in carrying out PROTAC R&D projects. We can provide products with different purity and length according to customer needs, and provide a full range of support services for your R&D projects.

• Functionalized PEG linker custom development
• PROTAC PEG linker synthesis
• PEG linker conjugates synthesis
• Characteristic evaluation and safety evaluation
• Assay development and screening

Our PEG Solution Service Workflow

What Can We Offer?

• One-stop development solutions
• Responsive project management
• Professional and skilled research team
• Rich experience in pegylation technology
• Well-equipped comprehensive analytical support
• Pilot and commercial scale production

BOC Sciences specializes in the development and manufacture of high-quality PEG products and derivatives, as well as related custom synthesis and PEGylation services. In addition, we provide customized one-stop solutions for various industries involving PEG needs, including the manufacture and supply of PEG linkers for PROTAC synthesis. If you are interested in our PEG solutions in PROTAC, please contact us to learn more.

References

1. Sun, X. et al. PROTACs: great opportunities for academia and industry. Signal Transduct Target Ther. 2019, 4: 64.
2. Troup, R.I. et al. Current strategies for the design of PROTAC linkers: a critical review. Explor Target Antitumor Ther. 2020, 1: 273-312.