Synthesis, photophysical, photochemical and biological properties of caged GABA, 4-[[(2H-1-benzopyran-2-one-7-amino-4-methoxy) carbonyl] amino] butanoic acid.
The photorelease of a caged neurotransmitter can be used to investigate the function of neuronal circuits in tissues. We have designed and synthesized a stable, caged gamma-aminobutyric acid (GABA) derivative, 4-[[(2H-1-benzopyran-2-one-7-amino-4-methoxy)carbonyl]amino] butanoic acid (BC204), that releases the neurotransmitter in physiological medium when irradiated with UV light at 300-400 nm in PBS at pH 7.4. The release of GABA occurs with the formation of the major photoproduct, 7-amino-4-(hydroxymethyl)-2H-1-benzopyran-2-one, via a solvolytic photodegradation mechanism of the coumarin moiety and was confirmed by electrospray mass spectrometry/mass spectrometry (ESI MS/MS). BC204 is chemically stable and shows no intrinsic activity after many hours under physiological dark conditions. These properties suggest that BC204 is an excellent form of caged GABA that is well suited for long-term biological studies.
Cürten
Beate
B
Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Kullmann
Paul H M
PH
Bier
Mark E
ME
Kandler
Karl
K
Schmidt
Brigitte F
BF
D003374:Coumarins / Q000737:chemistry; D004355:Drug Stability; D015394:Molecular Structure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010777:Photochemistry; D010782:Photolysis; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
C504213:4-(((2H-1-benzopyran-2-one-7-amino-4-methoxy)carbonyl)amino) butanoic acid; D003374:Coumarins; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid