Amino acids (AAs) are small polar molecules that are essential for life, as they play many roles in cells, e.g. cell signaling, protein synthesis, etc. Most of these functions require the prior absorption of AAs into cells, which is facilitated by AA transporters that are found in the cell membrane. Alterations in the transport of AAs are related to several human diseases, such as cancer, aminoacidurias and neurodegenerative diseases.
Therefore, from a human health perspective, there is a considerable interest in developing systems that could modulate the AA transport activity. In our study, we regulate AA transport by inhibiting human LAT2 transporter through a novel approach using small-molecule inhibitors that were obtained by virtual screening based on the structure of a novel prokaryotic AA transporter recently described in Prof. Manuel Palacín’s lab. In addition, we report a novel multidisciplinary strategy to modulate AA transport using a calixpyrrole as a synthetic transporter. Based on calixpyrrole anionophores, our transporter was synthesized in Prof. Pablo Ballester's Lab. Anion transport studies in large unilamellar vesicles (LUVs) reveal that preincorporation during vesicle preparation is the most efficient delivery strategy to insert our calix into lipid bilayers. In vitro experiments show that our calixpyrrole can transport L-Pro across cell membrane models (mainly LUVs). Moreover, experiments in HeLa cells show that our calixpyrrole is able to modulate L-Pro transport across the membrane of living systems.
From this research, new potential applications in biomedical research may arise, such as cell therapy and delivery of AA-derived drugs and prodrugs.
Major project supervisor
Minor project supervisor