Solution and gas phase hydrogen/deuterium exchange of oligoamide complexes by nanoelectrospray mass spectrometry

Hydrogen bonding is crucial to biological systems and is intrinsic to non-covalent interactions. They are important in the formation of higher order structures of proteins as well as in the interactions of proteins with other biological molecules. Electrospray ionization (ESI) is an important tool in the study and characterization of molecular complexes and has proven to be extremely powerful and invaluable in the studying of biomolecular structures and non-covalent interactions. We have utilized solution and gas phase hydrogen/deuterium exchange (HDX) as a method to determine the specificity of supramolecular complex formation using monomers possessing sites containing hydrogen-bond donor and acceptor groups. By comparing the average number of exchanges for the monomer subunits to the average number of exchanges for the complex, we can distinguish if a specific complex is formed in solution, or whether it is the artifact of a gas phase process during ESI. In this paper we have investigated several non-covalent supramolecular complexes by nanoelectrospray (nanoESI) mass spectrometry (MS). By using the solution and gas phase HDX, we were able to identify several specific supramolecular complexes. Thus, solution and gas phase HDX combined with nanoESI-MS provides for a convenient method in ascertaining the origin and stability of non-covalent complexes.