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Abstract: Identification of monosaccharide derivatives using an analytical technique is difficult due to their isomeric structures and similar physical properties. Although mass spectrometry (MS) has emerged as a prominent technique for this purpose, a comprehensive MS‐based method for analyzing diverse monosaccharide species is yet to be developed. Herein, we employ host‐guest chemistry using cucurbit[7]uril (CB[7]) with MS to identify four different monosaccharide derivative species. Tandem MS analysis distinguishes the monosaccharide derivatives based on the unique fragmentation pattern produced when forming gas‐phase complexes with CB[7]. The ion mobility studies combined with computational calculations reveal that subtle differences in isomers cause distinct orientations inside CB[7] cavity, resulting in different fragmentation patterns of the isomers. This unique study demonstrates that host‐guest chemistry combined with MS can be used for developing effective isomer analysis techniques. [ABSTRACT FROM AUTHOR]

Achieving strong host-guest interactions between synthetic hosts and hydrophilic guests in solution is challenging because solvation effects overwhelm other effects. To resolve this issue, we transferred complexes of cucurbit[7]uril (CB[7]) and monosaccharides to the gas phase and report here their intrinsic host-guest chemistry in the absence of solvation effects. It was observed that effective host-guest interactions in the gas phase mediated by ammonium cations allow the differentiation of the monosaccharide isomers in complex with CB[7] upon vibrational excitation. The potential of the unique observation was extended to a quantitative supramolecular analytical method for the monosaccharide guests. The combination of host-guest chemistry and phase transfer presented in this study is an effective approach to overcome current limitations in supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are insoluble protein aggregates comprised of highly ordered β-sheet structures and they are involved in the pathology of amyloidoses, such as Alzheimer's disease. A supramolecular strategy is presented for inhibiting amyloid fibrillation by using cucurbit[7]uril (CB[7]). CB[7] prevents the fibrillation of insulin and β-amyloid by capturing phenylalanine (Phe) residues, which are crucial to the hydrophobic interactions formed during amyloid fibrillation. These results suggest that the Phe-specific binding of CB[7] can modulate the intermolecular interaction of amyloid proteins and prevent the transition from monomeric to multimeric states. CB[7] thus has potential for the development of a therapeutic strategy for amyloidosis. [ABSTRACT FROM AUTHOR]

Amyloid fibrillation of the amyloidogenic proteins insulin and β‐amyloid is inhibited by cucurbit[7]uril (CB[7]) through host–guest interactions. In their Communication on page 7461 ff., K. Kim, H. I. Kim, and co‐workers demonstrate that CB[7] exhibits high binding affinity for phenylalanine residues, which are crucial to the hydrophobic interactions formed during amyloid fibrillation. This supramolecular strategy has potential for the development of a therapeutic agent for amyloidosis. [ABSTRACT FROM AUTHOR]

Die Bildung von Fibrillen aus Insulin und β ‐ Amyloid wird von Cucurbit[7]uril (CB[7]) über Wirt ‐ Gast ‐ Wechselwirkungen verhindert. In ihrer Zuschrift auf S. 7591 ff. demonstrieren K. Kim, H. I. Kim und Mitarbeiter, dass CB[7] hoch affin an Phenylalaninreste bindet, die entscheidend für die hydrophoben Wechselwirkungen während der Amyloidfibrillenbildung sind. Diese supramolekulare Strategie könnte zur Entwicklung von Amyloidosetherapeutika genutzt werden. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS)-based analysis using enzymatic digestion is widely used for protein sequencing and characterization. The large number of peptides generated from proteolysis, however, suppresses the signal of peptides with low ionization efficiency, thus precluding their observation and analysis. This study describes a technique for improved analysis of peptic peptides by adding the synthetic receptor cucurbit[7]uril (CB[7]), which binds selectively to peptides with N-terminal aromatic residues. Capturing the N-terminal phenylalanine (Phe) of peptides using CB[7] enhances the peptide abundances both in electrospray ionization MS and in matrix-assisted laser desorption ionization MS. Moreover, collision-induced dissociation (CID) of the CB[7]·peptide complex ions generates b- and y-type fragment ions with higher sequence coverage than those generated with uncomplexed peptides. The signal enhancement mediated by CB[7] is attributed to an increase in the peptide proton affinities upon CB[7] complexation. The mechanistic details of the fragmentation process are discussed on the basis of the structures of the complex ions obtained from ion mobility (IM) measurements and molecular modeling. This study demonstrates a novel and powerful approach to the enhancement of protein and peptide analysis using a synthetic receptor, without the need for new instrumentation, chemical modifications, or specialized sample preparation. The simplicity and potential generality of this technique should provide a valuable asset in the toolbox of routine protein and peptide analysis. [ABSTRACT FROM AUTHOR]