Structural determinants of substrates and inhibitors: probing glutamate transporters with 2,4-methanopyrrolidine-2,4-dicarboxylate

Bioorg Med Chem Lett. 1998 Nov 3;8(21):3101-6. doi: 10.1016/s0960-894x(98)00560-5.

Abstract

Using an intramolecular [2 + 2] photocyclization, 2,4-methanopyrrolidine-2,4-dicarboxylate was prepared as a conformationally locked analogue of glutamate. This compound, in combination with two other pyrrolidine dicarboxylates, has been used to define the structural elements that differentiate substrate and nonsubstrate inhibitors of a high-affinity, sodium-dependent glutamate transporter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors*
  • Amino Acid Transport System X-AG
  • Animals
  • Dicarboxylic Acids / chemical synthesis*
  • Glutamic Acid / analogs & derivatives*
  • Male
  • Molecular Conformation
  • Pyrrolidines / chemical synthesis*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • 2,4-methanopyrrolidine-2,4-dicarboxylate
  • ATP-Binding Cassette Transporters
  • Amino Acid Transport System X-AG
  • Dicarboxylic Acids
  • Pyrrolidines
  • Glutamic Acid