Evaluation of amino acid-mustard transport as L-type amino acid transporter 1 (LAT1)-mediated alkylating agents

Ken Ichi Hosoya, Hirokazu Kyoko, Naoki Toyooka, Atsushi Kato, Masahiro Orihashi, Masatoshi Tomi, Masanori Tachikawa

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


The L-type amino acid transporter 1 (LAT1, SLC7A5) is an Na +-independent neutral amino acid transporter the expression of which is located in retinal endothelial cells. Due to its broad substrate selectivity, LAT1 has been proposed to mediate the transport of amino acid-related drugs across the blood-tissue barriers. Here, we have investigated the transport screening of amino acid-mustards using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) which expresses LAT1. We synthesized 5 amino acid-mustards: tyrosine-mustard, phenylglycine-mustard, alanine-mustard, ornithine-mustard, and lysine-mustard. LAT1-mediated [3H]L- phenylalanine (Phe) uptake by TR-iBRB2 cells was inhibited in a competitive manner by tyrosine-mustard and phenylglycine-mustard as well as melphalan (phenylalanine-mustard). Phenylglycine-mustard was able to induce the efflux of [3H]Phe preloaded into the TR-iBRB2 cells expressing LAT1 through the obligatory exchange mechanism, although tyrosine-mustard, alanine-mustard, ornithine-mustard, lysine-mustard, and melphalan did not induce any significant efflux. These findings suggest that phenylglycine-mustard is a better substrate for LAT1 than melphalan and other amino acid-mustards.

Original languageEnglish
Pages (from-to)2126-2130
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Issue number11
Publication statusPublished - 2008 Nov
Externally publishedYes


  • Alkylating agent
  • Amino acid-mustard
  • Inner blood-retinal barrier
  • L-type amino acid transporter 1
  • Transport

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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