An Enantioselective Fluorescence Sensor for Glucose Based on a Cyclic Tetrapeptide Containing Two Boronic Acid Binding Sites

Abstract

The synthesis and binding properties of carbohydrate receptor 1d, which contains two boronic acid binding sites facing each other at opposing sides of a cyclotetrapeptide cavity, are presented. According to electrospray mass spectrometry, 1H NMR spectroscopy, and fluorescence spectroscopy, this receptor forms stable 1:1 complexes with D‐glucose (Ka = 24800 ± 1200 M–1) and L‐glucose (Ka = 11900 ± 1600 M–1) in water/methanol (1:1) at pH = 11.7. Complexes with D‐galactose, D‐mannose, and D‐allose are significantly less stable, while D‐fructose, D‐ribose, and D‐xylose cannot be bound by cooperative action of both boronic acid binding sites. Thus, 1d possesses high affinity and selectivity in glucose recognition combined with good enantioselectivity. Moreover, fluorescence of 1d is quenched upon substrate binding, which allows the use of this receptor as an optical sensor for glucose in aqueous solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Carbohydrate recognition by boronolectins, small molecules, and lectins

“…Stereochemical and regiochemical factors play important roles in the selective detection of saccharides with boronic acid-based sensors 44,189,267,268. Several research groups have been working on examining the stereochemical issues in binding.…”

“…The Kubik lab synthesized and examined the binding affinities of carbohydrate sensor 37 (Figure 12), which contains two boronic acid moieties on the opposite ends of a cyclic tetrapeptide 44. Fluorescent binding studies showed good enantioselectivity of sensor 37 for D-glucose ( K a = 24800 ± 1200 M −1 ) to L-glucose ( K a = 11900 ± 1600 M −1 ) in water/methanol (1:1, pH =11.7).…”

“…We have termed these boronic acid-based carbohydrate sensors/binders as boronolectins because they mimic the function of lectins and contain the boronic acid unit 36. Therefore, there are small molecule boronolectins (SBL),33,155,156 peptidoboronolectins (PBL),44,157–159 and nucleic acid-based boronolectins (NBL) 66,137. There has also been effort in taking advantage of non-covalent interactions such as hydrophobic, hydrogen bond, and ionic interactions,160 and interactions with metals for the design of carbohydrate receptors 34,82,161.…”

The binding of boronated peptides to low affinity mammalian saccharides

“…Kubik et al and Ravoo and Otremba have reported monosaccharide binding to diboronated cyclic peptides. In these cases, the peptides serve as structural scaffolds that project boronic acids in certain restricted orientations, and there is limited opportunity for amino acid sidechains to influence carbohydrate binding.…”

“…Amongst the receptors that use covalent interactions, boronic acid‐containing compounds have been the most extensively explored because of their ability to rapidly and reversibly associate with 1,2‐ and 1,3‐diol functionalities present on many sugars . Borono‐lectins or boronic acid‐containing compounds designed to be small molecule mimics of lectins, are now receiving heightened interest from molecular recognition researchers …”