Controlled band dispersion for quantitative binding determination and analysis with electrospray ionization‐mass spectrometry

Abstract

This review discusses recent emerging techniques that have been used to couple flow-injection analysis (FIA) and electrospray ionization-mass spectrometry (ESI-MS) for the quantitation of noncovalent binding interactions. Focus is placed predominantly on two such methods. Diffusion-based measurements, developed by Konermann and co-workers, uses controlled-band dispersion prior to ESI-MS to determine diffusion constants and binding constants based on the temporal variation of ligand signal measured in the mass spectrum (an indirect technique). Dynamic titration, developed by Schug and co-workers, is a direct method, where a temporal compositional gradient of a guest molecule is induced in the presence of host in solution to monitor the concentration dependence of complex formation as a function of observed complex ion abundance after ESI-MS. Further discussion places these techniques in the context of a variety of other direct and indirect ESI-MS-based binding determination methods, and highlights advantages, disadvantages, and practical considerations for their proper use to investigate a broad range of macromolecular and small-molecule interaction systems.

Intrinsic Properties of α-Cyclodextrin Complexes with Benzoate Derivatives in the Gas Phase: An Experimental and Theoretical Study

“…Electrospray ionization mass spectrometry (ESI–MS) has been intensively applied as a rapid and powerful analytical tool to screen for host–guest complexes. − However, the specific mass-to-charge ratios ( m / z ) of the detected species may serve to quickly determine their stoichiometries , but these observations alone do not provide any structural information. Compared with the generally accepted conceptions regarding CD complexation in solution, the nature of such host–guest complexes in the gas phase remains ambiguous or even controversial.…”

The Coupling of Taylor Dispersion Analysis and Mass Spectrometry to Differentiate Protein Conformations

“…Characterizing the noncovalent interactions between ligands and target proteins is essential in studying protein bioactivities, as well as in drug developments . Some TDA-MS methods were applied to related research. − To demonstrate the capability of our TDA-MS-based method, we investigated the interactions of tri- N -acetylchitotriose with lysozyme and cytochrome C. TDA-MS experiments were carried out at the following conditions: 50:15 cm length ratio (50 μm i.d.) branched capillaries were chosen; samples were diluted in 20 mM ammonium acetate aqueous solution at pH = ∼ 7 and injected into the system at a speed of 20 μL/h for 0.03 min; flow rate of the buffer were set at 1.2 mL/h (20 μL/min) during TDA analysis.…”

Determination of Noncovalent Binding Using a Continuous Stirred Tank Reactor as a Flow Injection Device Coupled to Electrospray Ionization Mass Spectrometry

“…To improve throughput, Fryčák and Schug developed a different titration method that uses a single solution of host and guest and is based on controlled band-dispersion [24,25,32,33]. The controlled band-dispersion concept appeared together with the development of flow injection analysis.…”

“…The product of the reaction is measured in the detector placed downstream. The use of FIA and controlled dispersion for MS-based binding determinations has been termed dynamic titration [24,25,32,33]. This method involves the injection of the guest solution into a flowing stream.…”