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Deodato D, Asad N, Dore TM. Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation. Org Biomol Chem. 2021;19(25):5589-5594doi: 10.1039/d1ob01006a.
Deodato, D., Asad, N., & Dore, T. M. (2021). Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation. Organic & biomolecular chemistry, 19(25), 5589-5594. https://doi.org/10.1039/d1ob01006a
Deodato, Davide, et al. "Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation." Organic & biomolecular chemistry vol. 19,25 (2021): 5589-5594. doi: https://doi.org/10.1039/d1ob01006a
Deodato D, Asad N, Dore TM. Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation. Org Biomol Chem. 2021 Jun 30;19(25):5589-5594. doi: 10.1039/d1ob01006a. PMID: 34086030.
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Org Biomol Chem. 2021 Jun 30;19(25):5589-5594. doi: 10.1039/d1ob01006a.

Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation.

Organic & biomolecular chemistry

Davide Deodato, Naeem Asad, Timothy M Dore

Affiliations

  1. New York University Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates. [email protected].
  2. New York University Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates. [email protected] and Department of Chemistry, University of Georgia, Athens, GA 30602, USA.

PMID: 34086030 DOI: 10.1039/d1ob01006a

Abstract

We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δu) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.

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