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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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When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
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EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
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Related Experiment Video

Updated: Jul 5, 2025

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
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Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

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DegraderTCM: A Computationally Sparing Approach for Predicting Ternary Degradation Complexes.

Paolo Rossetti1, Giulia Apprato1, Giulia Caron1

  • 1University of Torino, Department of Molecular Biotechnology and Health Sciences, CASSMedChem, Piazza Nizza 44, 10126 Torino, Italy.

ACS Medicinal Chemistry Letters
|January 17, 2024
PubMed
Summary

DegraderTCM is a new computational tool that models proteolysis targeting chimera (PROTAC) ternary complexes. This method aids in designing PROTAC drugs by predicting degradation activity and structure-activity relationships.

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Area of Science:

  • Biochemistry and Structural Biology
  • Computational Chemistry and Drug Design
  • Medicinal Chemistry

Background:

  • Proteolysis targeting chimeras (PROTACs) are an emerging therapeutic strategy inducing targeted protein degradation via ternary complex (TC) formation.
  • Understanding the 3D structure of PROTAC-TCS is essential for rational drug design.
  • Current methods for TC modeling can be computationally intensive.

Purpose of the Study:

  • To introduce DegraderTCM, a novel computational method for modeling PROTAC-mediated ternary complexes.
  • To validate the accuracy and efficiency of DegraderTCM.
  • To develop a predictive model for PROTAC degradation activity based on TC structure.

Main Methods:

  • Development of DegraderTCM, a computationally efficient method for PROTAC TC modeling.
  • Validation of DegraderTCM against experimentally determined TC structures.
  • Creation of a predictive model for PROTAC degradation activity using computed TC structures.

Main Results:

  • DegraderTCM provides accurate TC models with low computational cost and in a short time.
  • The method successfully predicted PROTAC degradation activity based on modeled TC structures.
  • Application of DegraderTCM to known PROTACs defined its applicability domain and revealed structure-activity relationships.

Conclusions:

  • DegraderTCM is a valuable tool for modeling PROTAC TCs and predicting degradation activity.
  • The method facilitates the rational design of novel PROTAC-based therapeutics.
  • DegraderTCM can be effectively utilized in the early stages of PROTAC drug discovery.