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

Journal of Drug Targeting
T OhnishiS Awazu

Abstract

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 technique. Glucose-coupled L-tyrosine (GcpY), which has a free carboxylic function, and 2-(L-tyrosylamide)-2-deoxy-D-glucose (Y-2DG), which has a free amino function were synthesized. The inhibitory effect of GcpY on [3 H]L-tyrosine 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 modified amino group is able to take a positive charge. Steric factors appeared to be relatively unimportant.

References

Nov 1, 1987·Journal of Neurochemistry·Q R SmithS I Rapoport
Mar 30, 1995·Biochemical Pharmacology·E G ChikhaleR T Borchardt
Sep 30, 1994·Biochemical and Biophysical Research Communications·T MizumaS Awazu
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·R J BoadoW M Pardridge

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Citations

Mar 1, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alessandro DalpiazStefano Manfredini
Dec 23, 2006·International Journal of Pharmaceutics·A DalpiazB Pavan

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