A Macrocyclic Tweezers‐Shaped Receptor for the Biomimetic Recognition of the Gal(α1‐3)Gal Disaccharide of the α‐Gal Antigen

The Gal(alpha 1-3)Gal is the terminal disaccharide unit of the alpha-Gal epitope [Gal(alpha 1-3)Gal(beta 1-4)GlcNAc], an exogenous antigenic determinant with several clinical implications, found in all non-primate mammals and in several dangerous pathogens, including certain protozoa and mycobacteria. Its absence in humans makes the alpha-Gal epitope an interesting target for several infectious diseases. Here we present the development of a macrocyclic tweezers-shaped receptor, resulting from the combination of the structural features of two predecessors belonging to the family of diaminocarbazole receptors, which exhibits binding properties in the low millimolar range toward the Gal(alpha 1-3)Gal disaccharide of the alpha-Gal antigen.The structural features of a macrocyclic receptor for axially substituted monosaccharides have been combined with those of a tweezers-shaped acylic receptor for all-equatorial disaccharides to generate a macrocyclic tweezers-like structure. The resulting structure features distinct recognition properties toward alpha Gal and the Gal(alpha 1-3)Gal disaccharide of the alpha-Gal antigen. image