Surface plasmon resonance spectroscopy for characterisation of membrane protein-ligand interactions and its potential for drug discovery
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- 作者：Simon G. Patching
- 关键词：ABC ; ATP binding cassette ; ADP ; Adenosine-5&prime ; -diphosphate ; AMP ; Adenosine-5&prime ; -monophosphate ; AMPPNP ; Adenosine-5&prime ; -(尾 ; 纬-imido)triphosphate ; ATP ; Adenosine-5&prime ; -triphosphate ; BACE1 ; 尾-Site amyloid precursor protein cleaving enzyme 1 ; BPM ; Biophysical Mapping ; CHAPSO ; 3-[(3-Cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate ; CMC ; Critical micelle concentration ; DDM ; n-Dodecyl-尾-d-maltoside ; EOT ; Extraordinary optical transmission ; EGF ; Epidermal growth factor ; GAB
- 刊名：Biochimica et Biophysica Acta (BBA)/Biomembranes
- 出版年：January, 2014
- 年：2014
- 卷：1838
- 期：1_part_PA
- 页码：43-55
- 全文大小：1258 K
文摘
Surface plasmon resonance (SPR) spectroscopy is a rapidly developing technique for the study of ligand binding interactions with membrane proteins, which are the major molecular targets for validated drugs and for current and foreseeable drug discovery. SPR is label-free and capable of measuring real-time quantitative binding affinities and kinetics for membrane proteins interacting with ligand molecules using relatively small quantities of materials and has potential to be medium-throughput. The conventional SPR technique requires one binding component to be immobilised on a sensor chip whilst the other binding component in solution is flowed over the sensor surface; a binding interaction is detected using an optical method that measures small changes in refractive index at the sensor surface. This review first describes the basic SPR experiment and the challenges that have to be considered for performing SPR experiments that measure membrane protein-ligand binding interactions, most importantly having the membrane protein in a lipid or detergent environment that retains its native structure and activity. It then describes a wide-range of membrane protein systems for which ligand binding interactions have been characterised using SPR, including the major drug targets G protein-coupled receptors, and how challenges have been overcome for achieving this. Finally it describes some recent advances in SPR-based technology and future potential of the technique to screen ligand binding in the discovery of drugs. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding.