Single‐Molecule Determination of the Isomers of d‐Glucose and d‐Fructose that Bind to Boronic Acids

• Published in: Angewandte Chemie 2018-03, Vol.130 (11), p.2891-2895
• Main Authors: Ramsay, William J., Bayley, Hagan
• Format: Article
• Language: English
• Subjects: Acids; Binding; Boronsäuren; Chemistry; Einzelmolekülverfahren; Esters; Fructose; Glucose; Isomers; Maltose; Monitoring; Monosaccharides; Nanoreaktoren; Porosity; Sugar; Variation; Zuckernachweis; α-Hämolysin
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201712740

Monosaccharides, such as d‐glucose and d‐fructose, exist in aqueous solution as an equilibrium mixture of cyclic isomers and can be detected with boronic acids by the reversible formation of boronate esters. The engineering of accurate, discriminating and continuous monitoring devices relies on knowledge of which cyclic isomer of a sugar binds to a boronic acid receptor. Herein, by monitoring fluctuations in ionic current, we show that an engineered α‐hemolysin (αHL) nanopore modified with a boronic acid reacts reversibly with d‐glucose as the pyranose isomer (α‐d‐glucopyranose) and d‐fructose as either the furanose (β‐d‐fructofuranose) or the pyranose (β‐d‐fructopyranose). Both of these binding modes contradict current binding models. With this knowledge, we distinguished the individual sugars in a mixture of d‐maltose, d‐glucose, and d‐fructose. Süß und sauer: Die reversible kovalente Verknüpfung von Boronsäuren mit Diolen lässt sich im Inneren eines Protein‐Nanoreaktors verfolgen. Der Ansatz kann diejenigen cyclischen Isomere von d‐Glucose und d‐Fructose identifizieren, die in wässriger Lösung an eine Boronsäure binden. Beide Bindungsmodi sind in gängigen Bindungsmodellen nicht vorgesehen.