Bioorganic & Medicinal Chemistry Letters 2010-01-01

Conformationally-restricted amino acid analogues bearing a distal sulfonic acid show selective inhibition of system [formula omitted]over the vesicular glutamate transporter

Jean-Louis G. Etoga, S. Kaleem Ahmed, Sarjubhai Patel, Richard J. Bridges, Charles M. Thompson, Jean-Louis G. Etoga, S. Kaleem Ahmed, Sarjubhai Patel, Richard J. Bridges, Charles M. Thompson

Index: Bioorg. Med. Chem. Lett. 20 , 2680-3, (2010)

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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.Copyright 2009 Elsevier Ltd. All rights reserved.