Identification of Ligands for Ion Channels: TRPM2.
Yushu GuMiaomiao LiuLinlin MaRonald J QuinnPublished in: Chembiochem : a European journal of chemical biology (2024)
Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, nonselective cation channel with a widespread distribution throughout the body. It is involved in many pathological and physiological processes, making it a potential therapeutic target for various diseases, including Alzheimer's disease, Parkinson's disease, and cancers. New analytical techniques are beneficial for gaining a deeper understanding of its involvement in disease pathogenesis and for advancing the drug discovery for TRPM2-related diseases. In this work, we present the application of collision-induced affinity selection mass spectrometry (CIAS-MS) for the direct identification of ligands binding to TRPM2. CIAS-MS circumvents the need for high mass detection typically associated with mass spectrometry of large membrane proteins. Instead, it focuses on the detection of small molecules dissociated from the ligand-protein-detergent complexes. This affinity selection approach consolidates all affinity selection steps within the mass spectrometer, resulting in a streamlined process. We showed the direct identification of a known TRPM2 ligand dissociated from the protein-ligand complex. We demonstrated that CIAS-MS can identify binding ligands from complex mixtures of compounds and screened a compound library against TRPM2. We investigated the impact of voltage increments and ligand concentrations on the dissociation behavior of the binding ligand, revealing a dose-dependent relationship.
Keyphrases
- mass spectrometry
- capillary electrophoresis
- liquid chromatography
- drug discovery
- high resolution
- multiple sclerosis
- ms ms
- binding protein
- gas chromatography
- ionic liquid
- bioinformatics analysis
- loop mediated isothermal amplification
- diabetic rats
- tandem mass spectrometry
- drug induced
- human health
- dna binding
- label free
- atomic force microscopy
- quantum dots
- brain injury
- real time pcr
- mild cognitive impairment
- subarachnoid hemorrhage