Surface plasmon resonance spectroscopy for characterisation of membrane protein–ligand interactions and its potential for drug discovery

Abstract

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.

Field-effect sensors – from pH sensing to biosensing: sensitivity enhancement using streptavidin–biotin as a model system

“…FET-sensors have the potential to offer ultrahigh sensitivity, low-cost production, portability and facile miniaturisation as part of a 'Lab-on-a-Chip'. FETsensors present several advantages in comparison with currently available label-free biosensors which operate via massdetection, 5,6 the electrical detection offered by FET-sensors provides additional information on, for example, conformational changes 7 or extracellular potentials. 8 In contrast to many other biosensing methodologies, FET-sensors do not require bulky optical measurement equipment.…”

Modelling and Characterization of the Sorption of Kynurenic Acid on Protein Surfaces

“…The temperature dependence of kinetics of the interaction between proteins and a drug molecule was detected to show that the values the k obs increase in significantly with the temperature and the relationship of K A and temperature (accurately reciprocal temperature) can be describable as a convex curve. Values for ΔH°, ΔS° and ΔCp of the interaction between the immobilized BSA and KYNA (8) were calculated to be −1.94 ± 0.25 kJmol -1 , 25.8 ± 0. [15,16,19] gives an evidence of the existing of specific binding affinity and way between KYNA and earliest investigated AMPA receptor peptide fragments.…”

“…6 shows the characteristics of equilibrium constant -temperature data pairs can be described as a convex curve. The thermodynamic parameters for binding interaction were obtained by nonlinear regression analysis with integrated van't Hoff equation (8) and are shown in Table 2. where ΔH 0 and ΔS 0 are the enthalpy and entropy change at the reference temperature, respectively, while ΔC p is the heat capacity change under standard conditions.…”

“…Chemical or physical adsorption onto the gold surface changes the refractive index of the dielectric, thereby the propagation constant of the surface plasmon is also changed [6]. Still, several research groups have published their results in the topic of characterization of different biomolecule interactions [7][8][9][10], but only a few articles offer deeper information on the temperature-dependent interactions between peptides or proteins and potential drug molecules by using SPR [11,12]. The objective of the present work was to provide complementary data on the interactions between serum albumins and KYNA by using only SPR experiments.…”

Block-Sequence-Specific Glycopolypeptides with Selective Lectin Binding Properties

“…42 In addition to RCA120, Galectin-3, a human galactose-specific lectin, was included. Galectin-3 contains carbohydrate recognition domains linked to non-lectin domains of about 130 amino acids.…”