Targeted protein degradation is a therapeutic strategy that involves the selective destruction of disease-causing proteins by exploiting the body's natural protein quality control machinery. This approach involves designing small molecules called "degraders" or "PROTACs" that can recruit the target protein to a complex containing an E3 ubiquitin ligase, leading to its ubiquitination and subsequent degradation by the proteasome.
The advantage of targeted protein degradation over traditional small molecule inhibitors is that it can remove the target protein from the cell completely, rather than simply blocking its activity. This can be particularly beneficial for proteins that are difficult to inhibit with small molecules, such as transcription factors or intracellular protein-protein interactions. Targeted protein degradation can lead to the identification of new drug targets or the development of novel therapeutic modalities.
Targeted protein degradation has shown promising results in preclinical studies and is currently being investigated for the treatment of various diseases, including cancer, neurodegenerative disorders, and genetic diseases. However, the approach is still in its early stages, and there are many challenges that need to be overcome, including identifying suitable E3 ligases, optimizing the design of degraders, and ensuring that the approach is safe and effective in humans.
ALL Chemistry Inc. provides custom targeted protein degradation (TPD) services that utilize advanced molecular biology techniques to selectively remove target proteins from cells. We can design and synthesize small molecules or other agents such as PROTACs (PROteolysis-TArgeting Chimeras) or molecular glues, which can specifically bind to the target protein and recruit an E3 ubiquitin ligase to trigger the degradation of the protein via the ubiquitin-proteasome pathway. The specific methods used may vary depending on the target protein and the desired outcome.
Custom TPD services include:
Proteolysis-targeting chimeras (PROTACs): PROTACs are small molecules that recruit an E3 ubiquitin ligase to a target protein, leading to its ubiquitination and subsequent degradation by the proteasome.
Hydrophobic tagging: This approach involves attaching a hydrophobic tag to a target protein, which then leads to its recognition and degradation by the proteasome.
CRISPR/Cas9-based protein degradation: This method involves using the CRISPR/Cas9 system to target and degrade specific proteins.
RNA interference (RNAi): RNAi involves the use of small interfering RNAs (siRNAs) to selectively knock down the expression of target proteins.
Overall, custom targeted protein degradation services can be a powerful tool for studying protein function and developing new therapies. However, it is important to carefully consider the potential off-target effects and other limitations of these methods before embarking on a project. ALL Chemistry Inc.'s custom TPD services can be tailored to meet the specific needs of each project. Some of the key services offered by us include target identification and validation, small molecule design and synthesis, cell-based assays to evaluate target engagement and protein degradation, and in vivo studies to assess efficacy and toxicity. Feel free to contact us for a consultation and proposal for your project.
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info@all-chemistry.com
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