A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc2 Disaccharide in Water

GlcNAc2 is the core disaccharide fragment present in N‐glycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because N‐glycans are directly involved in the docking of viruses to host cells, recognition of GlcNAc2 by a biomimetic receptor may be a convenient alternative to the use of lectins to interfere with viral entry and infection. Herein, we describe a simple biomimetic receptor recognizing the methyl‐β‐glycoside of GlcNAc2 in water with an unprecedented affinity of 160 μM, exceeding that of more structurally complex receptors reported in the literature. The tweezers‐shaped acyclic structure exhibits marked selectivity among structurally related disaccharides, and complete discrimination between mono‐ and disaccharides. Molecular modelling calculations supported by NOE data provided a three‐dimensional description of the binding mode, shedding light on the origin of the affinities and selectivities exhibited by the receptor. Think simple. In the development of biomimetic receptors for carbohydrates, an approach that focuses on simple acyclic architectures can be successfully exploited for disaccharide recognition, provided that the correct binding geometry can be achieved. Here we present a simple tweezers‐shaped receptor that selectively recognizes in water GlcNAc2, the core fragment of N‐glycans exposed on the surface of enveloped viruses, such as coronaviruses.