Ngamma-aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site.

Analogues of L-glutamine were designed and synthesized to test a hydrogen-bond hypothesis between ligand and neutral amino acid transporter ASCT2. The key design feature contains a substituted phenyl ring on the amide nitrogen that contains electron withdrawing and electron donating groups that alter the pKa of the amide NH. Through this study a preliminary binding site map has been developed, and a potent commercially available competitive inhibitor of the ASCT2 transporter has been identified.