title: Pseudopeptidic cages as receptors for N-protected dipeptides.
abstract: 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 ((1)H 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.
authors.affiliation: Departamento de Química Biológica y Modelización Molecular, Instituto de Química Avanzada de Cataluña (IQAC-CSIC) , Jordi Girona 18-26, E-08034 Barcelona, Spain.
authors.forename: Enrico
authors.initials: E
authors.lastname: Faggi
authors.forename: Alejandra
authors.initials: A
authors.lastname: Moure
authors.forename: Michael
authors.initials: M
authors.lastname: Bolte
authors.forename: Cristian
authors.initials: C
authors.lastname: Vicent
authors.forename: Santiago V
authors.initials: SV
authors.lastname: Luis
authors.forename: Ignacio
authors.initials: I
authors.lastname: Alfonso
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D014961:X-Ray Diffraction
chemical_list: D000596:Amino Acids; D004151:Dipeptides; D007097:Imines; D047028:Macrocyclic Compounds