Pseudopeptidic Cages as Receptors for N-Protected Dipeptides
Pseudopeptidic Cages as Receptors for N-Protected Dipeptides
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DOI：
10.1021/jo500629d
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发表时间：
2014-05-16
影响因子：
3.6
通讯作者：
Alfonso, Ignacio
中科院分区：
文献类型：
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作者：
Faggi, Enrico;Moure, Alejandra;Alfonso, Ignacio
短肽的分子识别是超分子化学中的一个挑战，而多肽类CAGE受体的使用代表了一种很有前途的方法。在这里，我们报道了一系列不同的假肽大环化合物的合成和表征，以及它们与N-保护的二肽的结合能力。作为高通量筛选，使用竞争ESI-MS实验对笼形宿主的二肽结合进行分析，以获得识别现象的总体趋势。此外，还在不同的溶剂中对选定的主体进行了核磁共振波谱(H-1核磁共振滴定和扩散有序光谱实验)的研究。结果明确地证明了[cage.二肽]超分子络合物的形成，并提供了关于相互作用强度的定量信息(K-ASS)。因此，识别出了产生更强和更具选择性的识别的伪肽笼状框架内的结构变量。这些笼子对N保护的二肽具有显著的选择性，这促使我们提出了一种基于极性和非极性非共价相互作用的结合模式。因此，在竞争激烈的介质中，我们面临着通过核磁共振和荧光光谱来识别模仿生物相关序列的目标二肽(Ac-EY-OH)的分子识别。
The molecular recognition of short peptides is a challenge in supramolecular chemistry, and the use of peptide-like cage receptors represents a promising approach. Here we report the synthesis and characterization of a diverse family of pseudopeptidic macrobicycles, as well as their binding abilities toward N-protected dipeptides using a combination of different techniques (NMR, ESI-MS, and fluorescence spectroscopy). The cage hosts were assayed for dipeptide binding using competition ESI-MS experiments as high-throughput screening to obtain general trends for the recognition phenomena. Selected hosts were additionally studied by NMR spectroscopy (H-1 NMR titration and diffusion-ordered spectroscopy experiments) in different solvents. The results unambiguously demonstrated the formation of the [cage.dipeptide] supramolecular complexes and rendered quantitative information about the strength of the interaction (K-ass). The structural variables within the pseudopeptidic cage framework that produced a stronger and more selective recognition were thus identified. The cages showed a remarkable selectivity for N-protected dipeptides with an aromatic amino acid at the carboxylic terminus, which prompted us to propose a mode of binding based on polar and nonpolar noncovalent interactions. Accordingly, we faced the molecular recognition of a target dipeptide (Ac-EY-OH) mimicking a biologically relevant sequence by NMR and fluorescence spectroscopy in highly competitive media.