Separation of combinatorial library isomers using ion mobility/mass spectrometry techniques

The ability to separate and identify molecules in a large mixture is a continuing challenge in the field of analytical chemistry. Although commercially available analytical methods, such as liquid chromatography (LC) and mass spectrometry (MS), have been successfully used, the added dimension of ion mobility spectrometry (IMS) can increase the number of molecules that can be separated and identified from a large mixture. The research that will be discussed involves the separation and identification of combinatorial peptide libraries using IMS techniques in conjunction with LC and MS. Peptide combinatorial libraries inherently contain sequence isomers (i.e. peptides that have the same set of amino acids but differ in sequence). Sequence isomers are isobaric and can not be uniquely identified using mass spectrometry alone. However, since the gas phase structures of sequence isomers often differ, IMS can separate these peptides.; The calculation of the first set of sequence-specific intrinsic size parameters from measured cross sections of sequence isomers will be presented. These parameters can be used to predict differences in the cross sections of sequence isomers. Another topic of discussion will be shifting mobilities of peptides via selective non-covalent binding of molecules. The use of collision induced dissociation (CID) to remove the non-covalently bound molecule, allows the original peptide to be observed at the shifted mobility. The analysis of large libraries by LC/IMS/CID/MS and the challenges that remain with this combined technique will also be discussed.