In this paper, we propose a new strategy for the development of synthetic amino acid transporters. Such molecules might be expected to display a wide range of biological activities and also find applications in drug delivery, metabolism regulation, and as next-generation antibiotics.
The transport of amino acids across biological membranes is vital for the proper functioning of every living cell. This is because at physiological pH amino acids are very polar (they have a positively charged N-terminus and a negatively charged C-terminus) and therefore cannot pass through lipid bilayers alone. In nature, amino acid transport is carried out by specialized membrane proteins that play important roles in regulating key physiological functions, such as protein biosynthesis, metabolism, gene expression, redox balance and signaling. The dysfunction of these proteins contributes to the development of serious diseases, such as diabetes, neurodegenerative disorders, obesity and cancer. Synthetic amino acid transporters could help in treating these diseases, and might also find applications in drug delivery, metabolism regulation, and as next-generation antibiotics.
Unfortunately, precisely because amino acids are both cations and anions, the development of such synthetic amino acid transporters has so far been extremely difficult, since it required combining both cation and anion binding sites in one structure. In this paper, however, we show that this is not the only possible strategy and that even very simple anion transporters are able to efficiently transport amino acids across lipid bilayers at physiological pH. To explain this unexpected effectiveness of simple anionophores, we developed a new assay for studying the transport of amino acids, that gave us insight into the mechanism of this phenomenon. As a result, we were able to propose a new strategy to search for synthetic amino acid transporters with improved properties and interesting biological activity. Read on here.