PROTAC Linker Design and Optimization

Inquiry

PROTAC Linker Design and Optimization

CD ComputaBio specialises in the design and optimisation of PROTAC linkers, making us a leader in the pharmaceutical industry. With cutting-edge technology and a team of dedicated experts, we offer a range of services tailored to meet the diverse needs of our clients. At CD ComputaBio, we specialize in designing and fine-tuning these linkers to achieve optimal PROTAC performance. Through a meticulous understanding of structure-activity relationships and a deep knowledge of chemical space, our team crafts linkers tailored to the specific requirements of each target, ensuring maximum efficacy and minimal off-target effects.

Introduction of Linker Design and Optimization

The essence of PROTAC technology lies in its ability to induce the degradation of target proteins by leveraging the cellular ubiquitin-proteasome system. This revolutionary approach offers advantages over traditional inhibition strategies by enabling the selective removal of disease-causing proteins. Central to the efficacy of PROTACs is the design and optimization of the linker connecting the binding moieties, dictating the proximity and orientation crucial for productive protein degradation.

Fig 1. Linker Design and OptimizationFigure 1. Linker Design and Optimization.( Manda S, et al.2020)

Our Service

Fig 2. PROTAC Linker Design

PROTAC Linker Design

  • Rational design of linker molecules based on target engagement profiles
  • Customization of linkers to enhance target specificity and cellular permeability
  • Integration of computational predictions and experimental validation for comprehensive design solutions

Fig 3. Linker Optimization

Linker Optimization

  • Iterative refinement of linker structures through molecular simulations and modeling
  • Evaluation of linker properties such as flexibility, length, and chemical composition
  • Fine-tuning for improved pharmacokinetic and pharmacodynamic profiles

Fig 4. Computational Analysis

Computational Analysis

  • Virtual screening of linker libraries for identifying promising candidates
  • Predictive modeling of PROTAC-target interactions to guide linker design
  • Assessment of ADMET properties to ensure safety and bioavailability

Fig 5. Consultation and Collaboration

Consultation and Collaboration

  • Expert advisory services for PROTAC design strategies and optimization approaches
  • Collaborative partnerships to integrate computational insights into experimental workflows
  • Tailored solutions to meet specific project requirements and timelines

The process of Linker Design and Optimization

Ligand Screening - We use virtual screening techniques to identify potential ligands for the target protein and E3 ligase.

Linker Design - Based on the selected ligands, we design a linker that is suitable for connecting the two ligands and ensuring optimal degradation of the target protein.

Linker Design and Optimization - Our experts employ rational design strategies, structure-based approaches, and machine learning algorithms to generate novel PROTAC linkers with enhanced efficacy, selectivity, and stability.

QSAR Analysis - We perform QSAR analysis to optimize the potency and selectivity of the PROTAC molecule.

Hit-to-Lead Optimization - We iteratively optimize the PROTAC molecule based on the results of our analyses to create a lead compound with desirable properties.

Approach to Linker Design and Optimization

Machine Learning and AI

Our use of machine learning algorithms and artificial intelligence accelerates the design process, enabling the prediction of optimal PROTAC structures and properties with high accuracy.

Fragment-Based Design

Through fragment-based design strategies, we assemble and optimize linker fragments to create PROTAC molecules that exhibit synergistic effects and enhanced target engagement.

Ligand-Based Design

We leverage ligand-based approaches to explore chemical space, identify key pharmacophore features, and design linkers that can optimize binding affinity and specificity.

Advantages of Our Services

Efficiency and Cost-Effectiveness

Our CADD approach accelerates the drug discovery process, reducing time-to-market and overall development costs associated with PROTAC research.

Precision and Customization

We offer tailored solutions based on specific project requirements, ensuring that PROTAC linkers are designed to meet unique therapeutic targets and molecular characteristics.

Expertise and Innovation

With a team of experienced computational biologists, chemoinformaticians, and drug design specialists, we bring a wealth of expertise and innovation to every project.

PROTAC linker design and optimization is a critical aspect of PROTAC development and requires expertise, precision, and innovation. At CD ComputaBio, we offer a comprehensive range of services for PROTAC linker design and optimization, utilizing advanced computational techniques to deliver customized solutions that meet your specific needs. Contact us today to learn more about how we can assist you in designing and optimizing PROTAC linkers for targeted protein degradation.

References:

  1. Manda S, Lee N K, Oh D C, et al. Design, synthesis, and biological evaluation of proteolysis targeting chimeras (PROTACs) for the dual degradation of IGF-1R and Src. Molecules, 2020, 25(8): 1948.
  2. Leissing T M, Luh L M, Cromm P M. Structure driven compound optimization in targeted protein degradation. Drug Discovery Today: Technologies, 2020, 37: 73-82.
* For Research Use Only.
Inquiry
logo
Give us a free call

Send us an email

Copyright © CD ComputaBio. All Rights Reserved.
  • twitter
Top