Related Experiment Video
Updated: Feb 9, 2026
15:05
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
9.3K
Deciphering Specificity Determinants for FR900359-Derived Gq α Inhibitors Based on Computational and
Raphael Reher1, Toni Kühl2, Suvi Annala3
1Institute of Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115, Bonn, Germany.
Chemmedchem
|June 7, 2018
Summary
Researchers explored chemical tools for targeting G protein-coupled receptors (GPCRs). They identified unique structural features in FR900359 analogs that inhibit Gqα, suggesting potential for developing new therapeutics.
Area of Science:
- Pharmacology
- Medicinal Chemistry
- Structural Biology
Background:
- Targeting intracellular Gα subunits of G protein-coupled receptors (GPCRs) with chemical tools is difficult.
- Novel therapeutic approaches require specific inhibitors for GPCR signaling pathways.
Purpose of the Study:
- To devise a strategy for elucidating characteristics that determine interactions with and inhibition of Gqα.
- To analyze novel FR900359-based analogs and known Gqα inhibitors.
Main Methods:
- 2D NMR spectroscopy to identify structural features.
- Molecular docking to analyze protein-ligand interactions.
- Comprehensive analysis of cyclic peptides and Gqα inhibitors.
Main Results:
- Unique macrocyclic structural features responsible for binding and inhibition of Gqα were identified.
- Novel compounds showed no effects on Gi and Gs proteins.
- No novel inhibitor surpassed the biological activity of FR900359.
Conclusions:
- FR900359 depsipeptides are valuable chemical tools for specific Gqα inhibition.
- These natural compounds serve as lead structures for developing novel Gα subunit inhibitors.
More Related Videos
Related Concept Videos
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
585
α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
Acarbose and miglitol are...
585
02:15Protein and Protein Structure
88.2K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
88.2K
01:14α-Halogenation of Carboxylic Acid Derivatives: Overview
4.1K
Unlike aldehydes and ketones, carboxylic acids do not readily participate in α halogenation reactions via enols or enolate intermediates. However, α-halogenated acids are obtained through other methods. One of the approaches is the Hell–Volhard–Zelinsky (HVZ) reaction, wherein the carboxylic acid is treated with halogen in the presence of PBr3. It involves the conversion of acid to acid halide, which exists in equilibrium with its enol form. The enol attacks the...
4.1K
01:52Eukaryotic Transcription Inhibitors
11.0K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
01:10Factors Affecting α-Alkylation of Ketones: Choice of Base
3.6K
α-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed by nucleophilic substitution. The choice of base employed is essential as it is the key factor in determining the reaction outcome.
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
3.6K
01:28Structures of Carboxylic Acid Derivatives
3.8K
Structure of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
3.8K