Blood-brain barrier transport of L-tyrosine conjugates: a model study for the brain targeting using large neutral amino acid transport system

We examined the relation ship between the charge of the amino or carboxylic function of a substrate and the substrate recognition by the large neutral amino acid (LNAA) transport carrier. using the in situ brain perfusion tec hnique. Glucose-coupled L-tyrosine (GcpY). which has a free carboxylic func tion, and 2-(L-tyrosylamide)-2-deoxy-D-glucose (Y-2DG), which has a free am ino function were synthesized. The inhibitory effect of GcpY on [H-3]L-tyro sine uptake was larger than that of N-methly-L-phenylalanine or N-acetyl-L- phenylalanine, whereas Y-2DG did not affect it. These results indicate that a free amino group is not required for recognition, provided that the modi fied amino group is able to take a positive charge. Steric factors appeared to be relatively unimportant.