Computer-Guided Design in Molecular Recognition: Design and Synthesis of a Glucopyranose Receptor

Abstract

Mit mehr als 400‐facher Selektivität wird Glucose gegenüber Galactose, Mannose und Fructose von einem Rezeptor erkannt, der mit dem Computerprogramm CAVEAT entworfen wurde. Dabei wurden die Boronsäurereste so positioniert, dass die Bildung cyclischer Boronate mit den Hydroxygruppen an den 1,2‐ sowie 4,6‐Positionen von α‐D‐Glucopyranose sehr leicht verläuft (siehe Bild). Die Fluoreszenz des Rezeptors nimmt nach Bindung von Glucose um 50 % ab.

Boronolectins and fluorescent boronolectins: An examination of the detailed chemistry issues important for the design

“…In this regard, spectroscopic methods used for the binding constant determination include CD, 52-60 absorption, 35,[61][62][63][64][65] and fluorescence. 26,31,[66][67][68][69][70][71][72][73][74][75][76] For example, Yoon and Czarnik determined the dissociation constant of anthrylboronic acid with D-fructose at pH 7.4 using fluorescence spectroscopy. 77 Titration of anthrylboronic acid (0.75 mM) at pH 7.4 with a polyol gives a dissociation constant of about 3.7 mM for D-fructose.…”

Boronic acid compounds as potential pharmaceutical agents

“…There are many other diol-containing compounds such as other sugars (e.g., fructose) and catechol type of compounds that can bind to boronic acid, quite often with higher affinity than glucose, and therefore may interfere with the desirable processes. 19 It would be desirable to use boronic acid compounds that have higher selectivity for glucose [112][113][114][115][116][117] for the construction of such glucoseresponse polymers.…”

Charge transfer fluorescent probes using boronic acids for monosaccharide signaling

“…Usually, bis-boronic acid derivatives show higher affinities and selectivities for D glucose in comparison with other sugar. [25][26][27][28] The emission properties of fluorescent probes based on a charge transfer mechanism show strong dependence on the polarity of the environment. In addition, some of these probes, especially the stilbene derivatives, can also show dependence on the viscosity of the environment.…”

“…Chelator groups and/or probes showing affinity for glucose from μM to hundred of mM have been reported. [25][26][27][28][29] In the same way, selectivity for glucose over the other sugars can be enhanced.…”