An enantioselective fluorescence sensor for glucose based on a cyclic tetrapeptide containing two boronic acid binding sites

The synthesis and binding properties of carbohydrate receptor Id, which contains two boronic acid binding sites facing each other at opposing sides of a cyclotetrapeptide cavity, are presented. According to electrospray mass spectrometry, H-1 NMR spectroscopy, and fluorescence spectroscopy, this receptor forms stable 1:1 complexes with D-glucose (K-a = 24800 +/- 1200 M-1) and L-glucose (K-a = 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, Id 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. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).