Conformationally-restricted amino acid analogues bearing a distal sulfonic acid show selective inhibition of system x(c)(-) over the vesicular glutamate transporter

  • Bioorg Med Chem Lett. 2010 Apr 15;20(8):2680-3. doi: 10.1016/j.bmcl.2009.10.020.
Jean-Louis G Etoga  1 ,  S Kaleem Ahmed ,  Sarjubhai Patel ,  Richard J Bridges ,  Charles M Thompson
Affiliations
  • 1. Department of Chemistry and Biochemistry, The University of Montana, Missoula, MT 59812, USA.
PMID: 20303751 DOI: 10.1016/j.bmcl.2009.10.020
Abstract

A panel of amino acid analogs and conformationally-restricted Amino acids bearing a sulfonic acid were synthesized and tested for their ability to preferentially inhibit the obligate cysteine-glutamate transporter system x(c)(-) versus the vesicular glutamate transporter (VGLUT). Several promising candidate molecules were identified: R/S-4-[4'-carboxyphenyl]-phenylglycine, a biphenyl substituted analog of 4-carboxyphenylglycine and 2-thiopheneglycine-5-sulfonic acid both of which reduced glutamate uptake at system x(c)(-) by 70-75% while having modest to no effect on glutamate uptake at VGLUT.

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