title: Screening of the binding of small molecules to proteins by desorption electrospray ionization mass spectrometry combined with protein microarray.
abstract: The interaction between bioactive small molecule ligands and proteins is one of the important research areas in proteomics. Herein, a simple and rapid method is established to screen small ligands that bind to proteins. We designed an agarose slide to immobilize different proteins. The protein microarrays were allowed to interact with different small ligands, and after washing, the microarrays were screened by desorption electrospray ionization mass spectrometry (DESI MS). This method can be applied to screen specific protein binding ligands and was shown for seven proteins and 34 known ligands for these proteins. In addition, a high-throughput screening was achieved, with the analysis requiring approximately 4 s for one sample spot. We then applied this method to determine the binding between the important protein matrix metalloproteinase-9 (MMP-9) and 88 small compounds. The molecular docking results confirmed the MS results, demonstrating that this method is suitable for the rapid and accurate screening of ligands binding to proteins. Graphical Abstract ᅟ.
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, People's Republic of China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Pharmacy, Changzhi Medical College, Changzhi, 046000, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, People's Republic of China.
authors.forename: Buqing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Cell Proliferation and Regulation Biology, Ministry of Education Beijing Normal University, Beijing, 100875, People's Republic of China.
authors.forename: Dacheng
authors.initials: D
authors.lastname: He
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Na
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, People's Republic of China. jinoyang@bnu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Ouyang
mesh_terms: D057166:High-Throughput Screening Assays / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins
keywords: Desorption electrospray ionization mass spectrometry; High-throughput screening; Protein ligand binding; Protein microarray