Synthesis and photoreactivity of caged blockers for glutamate transporters

• Published in: Bioorganic & medicinal chemistry letters 2003-03, Vol.13 (5), p.965-970
• Main Authors: Takaoka, Kiyo, Tatsu, Yoshiro, Yumoto, Noboru, Nakajima, Terumi, Shimamoto, Keiko
• Format: Article
• Language: English
• Subjects: Amino Acid Transport System X-AG - antagonists & inhibitors; Animals; Aspartic Acid - chemistry; Aspartic Acid - pharmacology; Biological and medical sciences; Biological Transport - drug effects; Cell Line; Coumarins - chemistry; Coumarins - pharmacology; Dogs; Drug Stability; Glutamic Acid - metabolism; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Photolysis; Spectrophotometry, Ultraviolet
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)01042-9

l-TBOA ( l- threo-β-benzyloxyaspartate) is, so far, the most potent non-transportable blocker for glutamate transporters. We synthesized α-CMCM- l-TBOA ( 1a) possessing [7-(carboxymethoxy)coumarin-4-yl]methyl ester as a caging group. α-CMCM- l-TBOA ( 1a) is biologically inactive until UV irradiation and the photolysis of 1a immediately released l-TBOA to show glutamate uptake inhibition. The photoreactivity of the coumarin-type caging group was superior to that of the o-nitrobenzyl-type caging group. The photolysis of α-CMCM- l-TBOA, a caged blocker for glutamate transporters, immediately released l-TBOA to show glutamate uptake inhibition.