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Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update

The oxidative stress response pathway is one of the hotspots of current pharmaceutical research. Many proteins involved in these pathways work through protein–protein interactions (PPIs). Hence, targeting PPI to develop drugs for an oxidative stress response is a promising strategy. In recent years,...

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Detalles Bibliográficos
Autores principales: Wu, Xuexuan, Zhang, Qiuyue, Guo, Yuqi, Zhang, Hengheng, Guo, Xiaoke, You, Qidong, Wang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025695/
https://www.ncbi.nlm.nih.gov/pubmed/35453304
http://dx.doi.org/10.3390/antiox11040619
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author Wu, Xuexuan
Zhang, Qiuyue
Guo, Yuqi
Zhang, Hengheng
Guo, Xiaoke
You, Qidong
Wang, Lei
author_facet Wu, Xuexuan
Zhang, Qiuyue
Guo, Yuqi
Zhang, Hengheng
Guo, Xiaoke
You, Qidong
Wang, Lei
author_sort Wu, Xuexuan
collection PubMed
description The oxidative stress response pathway is one of the hotspots of current pharmaceutical research. Many proteins involved in these pathways work through protein–protein interactions (PPIs). Hence, targeting PPI to develop drugs for an oxidative stress response is a promising strategy. In recent years, small molecules targeting protein–protein interactions (PPIs), which provide efficient methods for drug discovery, are being investigated by an increasing number of studies. However, unlike the enzyme–ligand binding mode, PPIs usually exhibit large and dynamic binding interfaces, which raise additional challenges for the discovery and optimization of small molecules and for the biochemical techniques used to screen compounds and study structure–activity relationships (SARs). Currently, multiple types of PPIs have been clustered into different classes, which make it difficult to design stationary methods for small molecules. Deficient experimental methods are plaguing medicinal chemists and are becoming a major challenge in the discovery of PPI inhibitors. In this review, we present current methods that are specifically used in the discovery and identification of small molecules that target oxidative stress-related PPIs, including proximity-based, affinity-based, competition-based, structure-guided, and function-based methods. Our aim is to introduce feasible methods and their characteristics that are implemented in the discovery of small molecules for different types of PPIs. For each of these methods, we highlight successful examples of PPI inhibitors associated with oxidative stress to illustrate the strategies and provide insights for further design.
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spelling pubmed-90256952022-04-23 Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update Wu, Xuexuan Zhang, Qiuyue Guo, Yuqi Zhang, Hengheng Guo, Xiaoke You, Qidong Wang, Lei Antioxidants (Basel) Review The oxidative stress response pathway is one of the hotspots of current pharmaceutical research. Many proteins involved in these pathways work through protein–protein interactions (PPIs). Hence, targeting PPI to develop drugs for an oxidative stress response is a promising strategy. In recent years, small molecules targeting protein–protein interactions (PPIs), which provide efficient methods for drug discovery, are being investigated by an increasing number of studies. However, unlike the enzyme–ligand binding mode, PPIs usually exhibit large and dynamic binding interfaces, which raise additional challenges for the discovery and optimization of small molecules and for the biochemical techniques used to screen compounds and study structure–activity relationships (SARs). Currently, multiple types of PPIs have been clustered into different classes, which make it difficult to design stationary methods for small molecules. Deficient experimental methods are plaguing medicinal chemists and are becoming a major challenge in the discovery of PPI inhibitors. In this review, we present current methods that are specifically used in the discovery and identification of small molecules that target oxidative stress-related PPIs, including proximity-based, affinity-based, competition-based, structure-guided, and function-based methods. Our aim is to introduce feasible methods and their characteristics that are implemented in the discovery of small molecules for different types of PPIs. For each of these methods, we highlight successful examples of PPI inhibitors associated with oxidative stress to illustrate the strategies and provide insights for further design. MDPI 2022-03-23 /pmc/articles/PMC9025695/ /pubmed/35453304 http://dx.doi.org/10.3390/antiox11040619 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wu, Xuexuan
Zhang, Qiuyue
Guo, Yuqi
Zhang, Hengheng
Guo, Xiaoke
You, Qidong
Wang, Lei
Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update
title Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update
title_full Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update
title_fullStr Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update
title_full_unstemmed Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update
title_short Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein–Protein Interactions: An Update
title_sort methods for the discovery and identification of small molecules targeting oxidative stress-related protein–protein interactions: an update
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025695/
https://www.ncbi.nlm.nih.gov/pubmed/35453304
http://dx.doi.org/10.3390/antiox11040619
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