A Rational Approach to the Design of Selective Substrates and Potent Nontransportable Inhibitors of the Excitatory Amino Acid Transporter EAAC1 (EAAT3). New Glutamate and Aspartate Analogues as Potential Neuroprotective Agents
journal contributionposted on 12.07.2001, 00:00 by Giuseppe Campiani, Meri De Angelis, Silvia Armaroli, Caterina Fattorusso, Bruno Catalanotti, Anna Ramunno, Vito Nacci, Ettore Novellino, Christof Grewer, Diana Ionescu, Thomas Rauen, Roger Griffiths, Colin Sinclair, Elena Fumagalli, Tiziana Mennini
Two three-dimensional receptor interaction models for EAAT substrates and nontransportable inhibitors have been developed, and new glutamate (Glu) and aspartate (Asp) analogues have been synthesized. The analogues 1a and 3 represent novel lead compounds for the development of EAAT substrates and nontransportable inhibitors, selective for EAATs over iGluRs, as possible neuroprotective agents useful to minimize the progression of chronic or acute neurodegenerative diseases. The role played by the protonatable amine function in the interaction with EAATs has been discussed.