Article
Chemistry, Multidisciplinary
Prashant Donthamsetti, David B. Konrad, Belinda Hetzler, Zhu Fu, Dirk Trauner, Ehud Y. Isacoff
Summary: G protein-coupled receptors (GPCRs) are common drug discovery targets, but the complexity of in vivo receptor activation has hindered drug development. Photopharmacology offers the potential to control drug action using light. Recent advances include a photoswitchable allosteric agonist that selectively activates receptors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Mark T. Agasid, Lars Sorensen, Leonhard H. Urner, Jun Yan, Carol Robinson
Summary: The use of mass spectrometry to study G protein-coupled receptors has revealed insights into sodium binding and ligand-induced changes, providing valuable information for understanding GPCR function.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kate F. Byrne, Ajay Pal, James F. Curtin, John C. Stephens, Gemma K. Kinsella
Summary: The focus of the review is on G-protein-coupled receptor (GPCR) targets, with chemokine, cannabinoid, and dopamine receptors showing promise. Further research is needed on potential targets such as MC4R, adhesion receptors, LPA, and Smo receptors to develop new drug-screening strategies for safe and effective GBM therapies.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Dekel David, Ziv Bentulila, Merav Tauber, Yair Ben-Chaim
Summary: GPCRs are involved in signal transduction processes, and although they span the cell membrane, they have not been considered to be regulated by membrane potential. Recent studies, however, have shown that several GPCRs are voltage regulated. This review discusses the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms, and the possible physiological roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Chemistry, Multidisciplinary
Xin-heng He, Chong-zhao You, Hua-liang Jiang, Yi Jiang, H. Eric Xu, Xi Cheng
Summary: G protein-coupled receptors (GPCRs) are important drug targets that play crucial roles in various physiological processes. Although extensive efforts have been made in the field of structural biology, a significant number of GPCR structures remain unsolved due to their structural instability. Recently, AlphaFold2 has been developed as a tool to predict the structure models of GPCRs and other functionally important proteins. However, our evaluation reveals several differences between the predicted models and experimental structures, such as the assembly of domains, shape of ligand-binding pockets, and conformation of binding interfaces. These differences hinder the use of predicted structure models in functional studies and structure-based drug design, where reliable high-resolution structural information is required.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Chemistry, Multidisciplinary
Xiaojing Cong, Wenwen Ren, Jody Pacalon, Rui Xu, Lun Xu, Xuewen Li, Claire A. de March, Hiroaki Matsunami, Hongmeng Yu, Yiqun Yu, Jerome Golebiowski
Summary: This study investigated how the amino-acid sequences of olfactory receptors (ORs) encode diversified responses to various ligands. Using a proteochemometric model, the researchers were able to predict OR responses to odorants and discover new OR-ligand pairs. This approach will contribute to the mapping of OR-odorant interactions and the identification of orphan receptors.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Juergen Bajorath
Summary: The study showed that introducing fluorine can significantly increase ligand potency, but the effect of fluorination on affinity varies depending on the fluorination position. Fluorination of the aromatic ring at the ortho position is favorable for potency enhancement, while fluorination of aliphatic fragments more often leads to a decrease in biological activity.
Article
Biochemical Research Methods
Jeffrey F. Diberto, Katie Smart, Reid H. J. Olsen, Bryan L. Roth
Summary: TRUPATH is a platform based on bioluminescence resonance energy transfer for quantifying G protein-coupled receptor activity via dissociation of heterotrimeric G protein biosensors. Protocols for agonist and antagonist TRUPATH assays in the 384-well plate format are provided, offering higher throughput capabilities.
Review
Biochemistry & Molecular Biology
Thian-Sze Wong, Guangzhi Li, Shiliang Li, Wei Gao, Geng Chen, Shiyi Gan, Manzhan Zhang, Honglin Li, Song Wu, Yang Du
Summary: Neuropsychiatric disorders are complex and have various causes. Finding effective treatment targets is difficult due to the heterogeneous nature of these diseases. However, the growing knowledge of G protein-coupled receptors (GPCRs) provides a potential avenue for drug discovery. Understanding the molecular mechanisms and structures of GPCRs can aid in the development of effective drugs. This review provides an overview of the role of GPCRs in neurodegenerative and psychiatric diseases, highlights new opportunities for GPCR targets, and discusses recent progress in GPCR drug development.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Miaomiao Qi, Xiang Liu, Ying Zhou, Haoyu Wang, Ying Zhao, Jing Ren, Jin Xiang
Summary: BBR is a modulator of GPER1 that inhibits the viability, migration, and autophagy of MDA-MB-231 cells, dependent on estrogen levels. It binds to GPER1 directly, changes its structure, and inhibits the NF-κB pathway, showing anti-cancer effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Yunfang Xiong, Ran Ke, Qingyu Zhang, Wenjun Lan, Wanjun Yuan, Karol Nga Ieng Chan, Tom Roussel, Yifan Jiang, Jing Wu, Shuai Liu, Alice Sze Tsai Wong, Joong Sup Shim, Xuanjun Zhang, Ruiyu Xie, Nelson Dusetti, Juan Iovanna, Nagy Habib, Ling Peng, Leo Tsz On Lee
Summary: This study reports the effective modulation of a GPCR for cancer treatment using small activating RNAs (saRNAs) for the first time. The saRNAs promote the expression of MAS1, a GPCR that counteracts cancer cell proliferation and migration. By enhancing MAS1 expression, these saRNAs suppress tumorigenesis and inhibit tumor progression in multiple cancer models. This research not only provides a new strategy for cancer therapy by targeting the renin-angiotensin system, but also offers a new avenue to modulate GPCR signaling through RNA activation.
Review
Engineering, Biomedical
Yuhong Jiang, Yuke Li, Xiujuan Fu, Yue Wu, Rujing Wang, Mengnan Zhao, Canquan Mao, Sanjun Shi
Summary: The translation article introduces the interaction between G protein-coupled receptors (GPCRs) and nanotechnology, as well as how nanotechnology can improve the efficacy and safety of GPCR-related drugs. Nanotechnology can encapsulate GPCR ligands to construct synthetic nano-GPCRs and precisely initiate sustained endosomal signal transduction through nanoparticles. Moreover, nanoparticles can enhance the potency of delivery systems by actively targeting specific cells through ligand-receptor binding and receptor-dependent endocytosis.
ACTA BIOMATERIALIA
(2023)