Aminopyrrolic Receptors for Molecular Recognition of Carbohydrates: Biological Activities and SAR Studies

Carbohydrates exert crucial roles in biological systems. For example, selective recognition of the glycoconjugates of the cell surface glycocalix is responsible for fundamental processes, like cell adhesion and infection by viruses and bacteria. Among the carbohydrates of biological interest, mannose has a central role in the infection mechanism by viruses of high health risk, such as HIV and HCV. Furthermore, mannose is highly expressed on the surface of pathogenic fungi and bacteria, representing therefore a target for new therapeutic strategies. Indeed, it has been shown that carbohydrate binding agents (CBAs) able to effectively recognize mannose epitopes exhibit antiviral and antifungal activity. Synthetic receptors are useful tools for understanding the molecular basis of the recognition phenomena occurring in Nature and represent potential CBAs for biological applications. In the last few years we have been involved in the design of synthetic receptors for the biomimetic recognition of carbohydrates and, in this context, we have developed a family of tripodal aminopyrrolic receptors that selectively recognize mannose in organic media. Microbiological essays vs. a selection of yeast and yeast-like highly mannosylated microorganisms showed that some members of the family possess antibiotic activity against pathogens like Candida and Prototheca, showing Minimum Inhibitory Concentration (MIC) values comparable to those of the most widely employed antifungal drugs. In this keynote lecture an overview of our studies will be presented, focusing on the structure-activity relationship emerging from systematic modifications of the receptor structure, and on the relationship between activity and mannose binding properties of the investigated molecules.