Pseudopeptidic Cages as Receptors for N-Protected Dipeptides

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• 作者：Enrico Faggi ; Alejandra Moure ; Michael Bolte ; Cristian Vicent ; Santiago V. Luis ; Ignacio Alfonso
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：May 16, 2014
• 年：2014
• 卷：79
• 期：10
• 页码：4590-4601
• 全文大小：550K
• 年卷期：v.79,no.10(May 16, 2014)
• ISSN：1520-6904

文摘

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 (¹H NMR titration and diffusion-ordered spectroscopy experiments) in different solvents. The results unambiguously demonstrated the formation of the [cage路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.