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 Xxx1-Xxx2-Xxx3-Xxx4 where Xxx1 = 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.

中文翻译：

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LC-IMS-CID-TOFMS技术的发展：256个组分的四肽组合文库的分析。

离子迁移率/飞行时间质谱技术的最新改进使掺入纳米流液相色谱和碰撞诱导解离技术成为可能。这种方法的组合为复杂系统的详细表征提供了一种新策略，例如组合库。我们的工作使用该技术对具有通用形式Xxx1-Xxx2-Xxx3-Xxx4的四肽文库进行详细分析，其中Xxx1 = Glu，Phe，Val，Asn；Xxx2 = Glu，Phe，Val，Tyr Xxx3 = Glu，Phe，Val，Th; Xxx4 = Glu，Phe，Val，Leu-一个有望包含256个不同肽序列的系统 结果证实了许多预期的肽序列的存在，并表明某些合成步骤似乎失败了。特别令人感兴趣的是在酪氨酸（Tyr）残基上观察到叔丁基保护基。似乎大多数带有该叔丁基的含Tyr肽都倾向于形成[2M + 2H] 2+二聚体，这很容易根据其气相迁移率的差异与[M + H] +单体区分开。在这种情况下，我们演示了使用[2M + 2H] 2+和[M + H] +离子之间的迁移率差异作为合成步骤失败的标志。