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.
Esslinger
C Sean
CS
NIH COBRE Center for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA. christopher.esslinger@umontana.edu
Cybulski
Kimberly A
KA
Rhoderick
Joseph F
JF
D026962:Amino Acid Transport System ASC / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D005973:Glutamine / Q000031:analogs & derivatives*; D006801:Humans; D006860:Hydrogen Bonding; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D015335:Molecular Probes
D026962:Amino Acid Transport System ASC; D015778:Minor Histocompatibility Antigens; D015335:Molecular Probes; C420506:SLC1A5 protein, human; D005973:Glutamine