Synthetic boronolectins for selective recognition of saccharides in aqueous media by spectrometric methods

CECILIA SAMANIEGO LOPEZ; NATALIA COSENZA; MARIA LAURA UHRIG; CARLA C. SPAGNUOLO

Villa General Belgrano

Simposio; GlycoAr 2016; 2016

CONICET

In the context of a main project to develop versatile fluorescent probes for relevant biologic analytes we describe the synthesis and sensing performance of boronolectins derived from benzoxaborole as receptors for saccharides and glycoconjugates. Boronic acids have been widely used for saccharide recognition through the formation of a reversible complex with diols. The dynamic covalent nature of this interaction has inspired research on different kinds of molecular and supramolecular systems with a wide variety of applications. Saccharide sensing has special interest in food industry, biological processes and as a diagnostic tool. In addition, the use of fluorescence emission as the reporter signal would lead to high rated molecules as potential sensors. Recently, we reported on a novel fluorescent probe for glycoconjugates with enhanced biocompatibility1: excitation/ emission in the near-infrared region (NIR) to achieve deep penetration in thick samples and reduced interference from auto-fluorescence of biomolecules and high water solubility in addition to very low citotoxicity. With this probe, we achieved detection of glycoproteins in vitro at the nanomolar level at pH 7.4 (physiological range) as well as selective labeling of the endoplasmic reticulum and Golgi system in vivo, known to be abundant in carbohydrates. Moving forward to the development of new probes with higher selectivity toward saccharides present on the membrane surface, we synthesized and studied the sensing performance of derivatives of benzoxaborole2, a boronic hemiester with good affinity for pyranoses over furanoses and much less explored as recognition unit for carbohydrates than common boronic acids. As proof of principle, we investigated the sensitivity of benzoxaborole analogs and a new divalent receptor combining benzoxaborole and benzeneboronic acid. By direct inspection of the changes in absorbance and fluorescence emission of the receptor unit upon binding of model carbohydrates and glycoproteins, such as glucose, mannose, N-acetylglucosamine, sialic acid, fucose, we could establish trends in binding affinity. Typically, the fluorescence emission of the benzoxaborole unit decreases with sugar binding. Interestingly, the divalent host is able to recognize sialic acid in an orthogonal manner due to the increase in the fluorescence emission observed while the other sugars caused depletion of the fluorescence intensity. In this work we present also binding studies through indicator displacement assays, and the prospect in construction of multivalent receptors derived from dendrimers and silica nanoparticles in order to achieve sensor platforms with enhanced sensitivity.