Recent improvements in ion mobility/time-of-flight mass spectrometry techniques have made it possible to incorporate nano-flow liquid chromatography and collision induced dissociation techniques. This combination of approaches provides a new strategy for detailed characterization of complex systems - such as, combinatorial libraries. Our work uses this technology to provide a detailed analysis of a tetrapeptide library having the general form Xxx 1-Xxx2-Xxx3-Xxx4 where Xxx 1 = Glu, Phe, Val, Asn; Xxx2 = Glu, Phe, Val, Tyr; Xxx3 = Glu, Phe, Val, Thr; and Xxx4 = Glu, Phe, Val, Leu - a system that is expected to contain 256 different peptide sequences. The results corroborate the presence of many expected peptide sequences and indicate that some synthetic steps appear to have failed. Particularly interesting is the observation of a t-butyl protecting group on the tyrosine (Tyr) residue. It appears that most Tyr containing peptides that have this t-butyl group attached favor formation of [2M + 2H]2+ dimers, which can be readily distinguished from [M + H]+ monomers based on differences in their gas-phase mobilities. In this case, we demonstrate the use of the mobility differences between [2M + 2H]2+ and [M + H] + ions as a signature for a failure of a synthetic step. © 2003 American Society for Mass Spectrometry.
Hilderbrand, A. E., Myung, S., Srebalus Barnes, C. A., & Clemmer, D. E. (2003). Development of LC-IMS-CID-TOFMS techniques: Analysis of a 256 component tetrapeptide combinatorial library. In Journal of the American Society for Mass Spectrometry (Vol. 14, pp. 1424–1436). Elsevier Inc. https://doi.org/10.1016/j.jasms.2003.08.002