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High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening | |
Qin, Shanshan1 ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |
2018 | |
Source Publication | CHEMICAL SCIENCE
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ISSN | 2041-6520 |
Volume | 9Issue:12Pages:3192-3199 |
Status | 已发表 |
DOI | 10.1039/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 By | SCI ; SCIE ; EI |
Funding Project | National Key Research and Development Program of China[2016YCF0905902] |
WOS Research Area | Chemistry |
WOS Subject | Chemistry, Multidisciplinary |
WOS ID | WOS:000428987200013 |
Publisher | ROYAL SOC CHEMISTRY |
EI Accession Number | 20181304957302 |
EI Keywords | Biological membranes ; Cell membranes ; Cytology ; Mass spectrometry ; Proteins ; Throughput |
EI Classification Number | Biological Materials and Tissue Engineering:461.2 ; Chemistry:801 ; Physical Chemistry:801.4 ; Organic Compounds:804.1 |
WOS Keyword | GLUCAGON-LIKE PEPTIDE-1 ; DRUG DISCOVERY ; LIGANDS ; BINDING ; GPCR ; INHIBITORS ; STABILITY ; DESIGN ; KINASE ; ASSAYS |
Original Document Type | Article |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/18249 |
Collection | iHuman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 Author | Wang, 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 Affilication | iHuman Institute |
Corresponding Author Affilication | School of Life Science and Technology; iHuman Institute |
First Signature Affilication | iHuman 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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