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Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

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It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
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The Proteasome02:18

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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Protein Complexes with Interchangeable Parts01:57

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
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Protein Networks02:26

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An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
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Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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Bifunctional robots inducing targeted protein degradation.

M Elizabeth Sobhia1, Harish Kumar1, Sonia Kumari1

  • 1Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector - 67, S. A. S. Nagar, Mohali, Punjab, 160062, India.

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Summary

Targeted Protein Degradation (TPD) using PROTACs (PROteolysis-TArgeting Chimeras) offers new therapeutic avenues. This review covers PROTAC design, AI-driven insights, and optimization for diverse diseases.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Targeted Protein Degradation (TPD) is an emerging therapeutic modality.
  • PROteolysis-TArgeting Chimeras (PROTACs) are bifunctional molecules that hijack the cell's ubiquitin-proteasome system to degrade specific proteins.
  • PROTACs demonstrate potential applications in oncology, neurodegenerative diseases, and infectious diseases.

Purpose of the Study:

  • To review recent advancements in PROTAC technology.
  • To summarize PROTAC design and development strategies, including linker optimization and molecular insights.
  • To explore the role of Artificial Intelligence (AI) in rationalizing ternary complex formation.

Main Methods:

  • Literature review of recent PROTAC research.
  • Analysis of PROTAC design principles, focusing on protein-ligand interactions and linker chemistry.
  • Inclusion of computational approaches, including AI (machine learning and deep learning), for ternary complex prediction.

Main Results:

  • Compilation of diverse PROTAC applications targeting various proteins.
  • Detailed summary of strategies for optimizing PROTAC chemical and pharmacokinetic properties.
  • Discussion on advanced PROTAC designs for complex protein targets.

Conclusions:

  • PROTACs represent a significant advancement in event-driven pharmacology.
  • The integration of AI and computational tools enhances PROTAC design and development.
  • Continued research in PROTAC chemistry and design promises broad therapeutic potential.