Linker Design and Optimization Services

* Please be kindly noted that our services and products can only be used for research to organizations or companies and not intended for any clinical or individuals.

We offer professional PROTAC Linker design and optimization services. Our services address the critical steps in Linker design for PROTAC drug development, solving challenges related to Linker issues in the drug development process. We aim to accelerate the drug development process and enhance drug performance.

What is The Linker?

The linker is responsible for linking two key domains of PROTAC: the domain that specifically binds to the target protein that needs to be degraded, and the domain that binds to the E3 ubiquitin ligase. To date, several types of connectors have been reported and used in the formation of PROTAC ternary complexes, such as PEG liner, alkyl liner and "click chemical" liner. It plays an important role in the effective ubiquitination and final degradation of target proteins.

Challenges We Help Solve

1. Insufficient Drug Activity: By optimizing parameters such as the length, flexibility, and rigidity of the Linker, we enhance the binding capability of PROTAC molecules with the target protein and E3 ligase, thereby improving the drug's activity.
2. Poor Stability: We design Linkers with higher chemical stability to reduce drug degradation in the body, extend the drug's half-life, and improve its stability.
3. Poor Selectivity: We optimize the Linker's structure to reduce the binding of PROTAC molecules to non-target proteins, enhancing drug selectivity and reducing side effects.
4. Solubility and Permeability Issues: By adjusting the hydrophilic/hydrophobic balance of the Linker, we improve the solubility and permeability of PROTAC molecules, thereby enhancing drug bioavailability.

Our Linker Design and Optimization Services

Linker Optimization

Structural Modification: We chemically modify existing Linkers by introducing specific functional groups or altering the linking methods to enhance their stability and biocompatibility.

Performance Evaluation and Iteration: We perform multi-dimensional evaluations of optimized Linkers, including activity, stability, and selectivity, and iteratively refine them based on the evaluation results.

Linker Screening

High-throughput Screening Platform: Utilizing high-throughput screening technology, we rapidly select the Linkers with the best performance from large Linker libraries.

Structure-based Screening: Using protein structural information, we apply affinity screening technologies (such as ASMS, SPR, etc.) to identify Linkers that best match the target protein and E3 ligase.

Linker Synthesis

Custom Synthesis: We provide high-quality Linker synthesis services, producing various types of Linkers according to customer requirements, ensuring high purity and quality.

Process Optimization: We continuously optimize the synthesis process to improve the synthesis efficiency and yield of Linkers, thereby reducing production costs.

Workflow of Linker Design and Optimization Services

1. Needs Communication: We have in-depth discussions with customers to understand their specific PROTAC drug development needs and goals.
2. Design and Optimization: Based on customer requirements, we design and optimize Linkers, offering multiple design options for customer selection.
3. Performance Evaluation: We evaluate the performance of the designed Linkers, including testing for activity, stability, and selectivity.
4. Delivery and Feedback: We deliver the optimized Linkers to customers and make further adjustments and optimizations based on their feedback.

Why Choose Our Services?

Professional Technical Team: Our team consists of experienced professionals with strong academic backgrounds and practical experience in PROTAC drug development.

Advanced Equipment and Technology Platforms: We are equipped with advanced experimental equipment and technology platforms that enable efficient Linker design, synthesis, and performance evaluation.

Rich Project Experience: We have extensive experience in PROTAC drug development and can offer personalized solutions to meet customer needs.

Strict Quality Control: We implement strict quality control to ensure that the Linkers provided are of high purity and quality.

Technology Platforms

Computer-Aided Drug Design (CADD) Platform: We use computational simulation techniques to predict and optimize the structure and performance of Linkers.

High-throughput Screening Platform: This platform allows us to rapidly screen a large number of Linkers to identify those with the best performance.

Synthesis and Analysis Platform: We conduct the synthesis and performance analysis of Linkers to ensure their quality and performance.

Frequently Asked Questions (FAQ)

1. How does Linker design affect the activity of PROTAC drugs?

Linker design significantly impacts PROTAC drug activity. Parameters such as the length, flexibility, and rigidity of the Linker influence the binding ability of PROTAC molecules to the target protein and E3 ligase, thereby affecting drug activity.

2. How can the stability of a Linker be improved?

Stability can be enhanced by selecting appropriate chemical bonds and functional groups, as well as optimizing the Linker's structure.

3. How does the length of the Linker affect the selectivity of PROTAC drugs?

The length of the Linker influences the spatial distance between the PROTAC molecule, target protein, and E3 ligase, thereby affecting drug selectivity. An optimal Linker length can improve drug selectivity and reduce side effects.

4. How do I choose the appropriate Linker length?

The appropriate Linker length should be selected based on the structural characteristics of the target protein and E3 ligase, as well as the specific needs of the drug development process. Generally, longer Linkers offer more spatial flexibility but may reduce stability, while shorter Linkers improve stability but may limit spatial flexibility.

References:

1. Ciechanover, A. (2003). The ubiquitin proteolytic system and pathogenesis of human diseases: a novel platform for mechanism-based drug targeting.
2. Churcher, I. (2017). Protac-induced protein degradation in drug discovery: breaking the rules or just making new ones? Journal of medicinal chemistry, 61(2), 444-452.

* PROTAC^® is a registered trademark of Arvinas Operations, Inc., and is used under license.