High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening
2018
Source PublicationCHEMICAL SCIENCE
ISSN2041-6520
Volume9Issue:12Pages:3192-3199
Status已发表
DOI10.1039/c7sc04698g
Abstract

G protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins and thus constitute an important family of therapeutic targets. Therefore, significant effort has been put towards the identification of novel ligands that can modulate the activity of a GPCR target with high efficacy and selectivity. However, due to limitations inherent to the most common techniques for GPCR ligand discovery, there is a pressing need for more efficient and effective ligand screening methods especially for the identification of potential allosteric modulators. Here we present a high-throughput, label-free and unbiased screening approach for the identification of small molecule ligands towards GPCR targets based on affinity mass spectrometry. This new approach features the usage of target-expressing cell membranes rather than purified proteins for ligand screening and allows the detection of both orthosteric and allosteric ligands targeting specific GPCRs. Screening a small compound library with this approach led to the rapid discovery of an antagonist for the 5-HT receptor and four positive allosteric modulators for GLP-1 receptor that were not previously reported.

Indexed BySCI ; SCIE ; EI
Funding ProjectNational Key Research and Development Program of China[2016YCF0905902]
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000428987200013
PublisherROYAL SOC CHEMISTRY
EI Accession Number20181304957302
EI KeywordsBiological membranes ; Cell membranes ; Cytology ; Mass spectrometry ; Proteins ; Throughput
EI Classification NumberBiological Materials and Tissue Engineering:461.2 ; Chemistry:801 ; Physical Chemistry:801.4 ; Organic Compounds:804.1
WOS KeywordGLUCAGON-LIKE PEPTIDE-1 ; DRUG DISCOVERY ; LIGANDS ; BINDING ; GPCR ; INHIBITORS ; STABILITY ; DESIGN ; KINASE ; ASSAYS
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/18249
CollectioniHuman研究所
iHuman研究所_特聘教授组_Andrej Sali组
iHuman研究所_特聘教授组_Raymond Stevens组
生命科学与技术学院_特聘教授组_王明伟组
iHuman研究所_PI研究组_刘志杰组
iHuman研究所_PI研究组_赵素文组
iHuman研究所_PI研究组_水雯箐组
生命科学与技术学院_博士生
Corresponding AuthorWang, Ming-Wei; Shui, Wenqing
Affiliation
1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
2.Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China
3.Chinese Acad Sci, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201202, Peoples R China
5.Univ N Carolina, Chapel Hill Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA
6.GPCR Consortium, San Marcos, CA 92078 USA
7.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
First Author AffilicationiHuman Institute
Corresponding Author AffilicationSchool of Life Science and Technology;  iHuman Institute
First Signature AffilicationiHuman Institute
Recommended Citation
GB/T 7714
Qin, Shanshan,Meng, Mengmeng,Yang, Dehua,et al. High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening[J]. CHEMICAL SCIENCE,2018,9(12):3192-3199.
APA Qin, Shanshan.,Meng, Mengmeng.,Yang, Dehua.,Bai, Wenwen.,Lu, Yan.,...&Shui, Wenqing.(2018).High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening.CHEMICAL SCIENCE,9(12),3192-3199.
MLA Qin, Shanshan,et al."High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening".CHEMICAL SCIENCE 9.12(2018):3192-3199.
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