Higher order structures of biomolecules investigated by capillary electrophoresis coupled with ion mobility mass spectrometry

The elucidation of structure-activity relationships and determination of higher order structures (HOS) of therapeutic oligonucleotides (ONs), aptamers, functional foods, and bio-active compounds retains attention of scientists. The higher order structures typically relies on spectroscopy methods in solution. However, mass spectrometry (MS) and ion mobility mass spectrometry (IM-MS) gains huge interest due to atom connectivities determination, identification and quantitation capabilities of (trace) organic compounds at high throughput.
Extrapolate data obtained from mass spectrometry (MS) and ion mobility mass spectrometry (IM-MS) to deduce HOS in solution requires validation. Here we propose the use of Capillary Electrophoresis (CZE, t-ITP, and KCE) on-line coupled with IM-MS, energy-resolved collision induced dissociation and collision induced unfolding to investigate the higher order structures of biomolecules in solution and the gas phase. Different models such as peptides, naturally occurring and chemically modified ONs investigated by CZE, t-ITP, and KCE coupled with IM-MS are discussed.