The interactions between cell-surface glycans and glycan binding proteins (GBPs) play important roles in cell-cell recognition and signal transduction. Understanding how sugar-encoded information is read and translated by natural GBPs provides potential applications in disease detection and therapy.[1] Artificial receptors that bind carbohydrates using noncovalent interactions are powerful tools to study the complex binding occurring on cell surfaces. Recently, our group reported a synthetic tetrapodal receptor that achieves high specificity for β-octyl mannopyranosides in choroform as a result of 2:1 and 1:2 receptor:sugar ratios that arise from multivalent and homotropic cooperative binding modes.[2] Specifically, the 2:1 receptor:sugar complex is a cage-like structure where only three of the four aminopyrrolitic arms of the receptor are involved in binding (Figure 1). In the current study, we make use of the fourth arm for further functionalization to develop the next generation of receptors. To improve the affinity and selectivity of the glycan recognition as well as achieve binding in aqueous solvents, new dimeric receptors with different lengths of ethylene glycol linkers were synthesized and characterized. These dimeric receptors are intended to mimic the C-type GBPs which bind carbohydrates in a Ca2+-dependent manner. To evaluate the recognition capabilities of demeric receptors several methyl pyranosides were selected as substrates, such as αGlc, βGlc, αGal, βGal, αMan, αGlcNAc, βGlcNAc, etc. The interactions of the receptors and the corresponding saccharides were investigated by mass spectrometry and 1H NMR titrations. The preliminary ESI-MS results revealed the favorable complexation between the dimeric hosts and carbohydrate guests and suggested the preference of dimeric receptors for β-anomers versus α-anomers. Furthermore, 1H NMR titrations showed the expected favorable binding capabilities and indicated interesting binding properties via Ca2+ modulation. We anticipate that new molecules could have impact for drug delivery, disease detection, and as therapeutics. [1] Han, X. et al. Current Opinion in biotechnology, 2014, 34, 41-47. [2] Rieth, S. et al. Chemical Science, 2013, 4, 357-367.

Carbohydrate recognition by Ca2+-dependent dimeric synthetic receptors

251st National Meeting (2016)

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