Probing the conformational changes during desolvation of ions using orthogonal mobility methods (CE-IM MS)

Routine analyses using Mass Spectrometry (MS) detection became a very popular due to the low limit of detection, great sensitivity, selectivity and specificity. Moreover MS enables structural elucidation and physical (or physicochemical) properties determination using low amount of not especially pure samples. One of these properties is substantially the stoichiometry determination of non-covalent complexes such as Ligand receptor systems (e.g. DNA-drugs, Hormones/drugs-receptor, quaternary structure arrangement of polypeptides, …). MS determination in native condition (Native MS) of this stoichiometry allows large scale screening of potential drugs candidates in pharmaceutical context. The addition of Ion-Mobility (IM) to mass spectrometry (IM-MS) with computational chemistry support allows the structural conformation monitoring (as Collisional Cross Section or CCS) and the elucidation of interactions of the non-covalent complexes. Nonetheless such determinations suppose/assume that desolvation steps and gas phase transfer during MS detection do not modify the tridimensional structure of these systems or the magnitude order of the involved interactions (dipole-dipole, dipole-ion, ion-ion, hydrophobic interactions). Further studies (Circular Dichroism, Nuclear Magnetic resonance, UV-Visible spectra …) are generally required to confirm the MS data but there are unfortunately time consuming.
This project proposes the coupling of Capillary Electrophoresis (CE) to IM-MS in order to obtain in one injection the quantitative and qualitative data of non-covalent complexes and the monitoring of tridimensional conformation modification between the liquid and gas phase. Indeed CE allows the determination of numerous physicochemical properties (dissociation constant, pK values, hydrodynamic radius determination …). The structural data (i.e. hydrodynamic radius and CCS) are compared to the data obtained by IM-MS as a proof of concept using tryptic digest of Bovine Serum Albumine (BSA).