Size does matter! Label-free detection of small molecule–protein interaction

Abstract

This review is focused on methods for detecting small molecules and, in particular, the characterisation of their interaction with natural proteins (e.g. receptors, ion channels). Because there are intrinsic advantages to using label-free methods over labelled methods (e.g. fluorescence, radioactivity), this review only covers label-free techniques. We briefly discuss available techniques and their advantages and disadvantages, especially as related to investigating the interaction between small molecules and proteins. The reviewed techniques include well-known and widely used standard analytical methods (e.g. HPLC-MS, NMR, calorimetry, and X-ray diffraction), newer and more specialised analytical methods (e.g. biosensors), biological systems (e.g. cell lines and animal models), and in-silico approaches.

Gold Nanoparticles Surface Plasmon Resonance Enhanced Signal for the Detection of Small Molecules on Split-Aptamer Microarrays (Small Molecules Detection from Split-Aptamers)

“…The main difficulty in such diagnostic relates to the small size and low concentrations of the encountered targets [4]. Direct detection is generally impossible as the effect of the binding of the targets to the probes is usually close to noise signal.…”

Optical Biosensors for Label-Free Detection of Small Molecules

“…Small molecules, in particular, are of great interest in pharmaceutical research, for example, because they can cross the blood-brain barrier. Detection of many drugs is diagnostically and clinically relevant but is also of interest in pharmaceutical sciences for drug screening and development of new biotherapeutics, as well as for studying the activity, kinetics, and stability of pharmaceuticals [10]. Therapeutic drug monitoring, which aims to optimize the pharmacological response of a drug while avoiding adverse effects, measures the drug concentrations in a biological matrix and with appropriate interpretation affects the prescribing procedures [11].…”

Label-free cytokine micro- and nano-biosensing towards personalized medicine of systemic inflammatory disorders

“…To this end, researchers usually use biopolymers to immobilize the protein in a controlled manner [39]. This approach also reduces non-specific adsorption of analytes to the sensor surface, thus enabling discrimination between specific and non-specific bindings [40]. The binding of the analytes changes the sensor surface property or the near-field environment of the sensor surface.…”