Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons. / Nørager, Niels Grøn; Jensen, Christel Barker; Rathje, Mette; Andersen, Jacob; Madsen, Kenneth Lindegaard; Kristensen, Anders Skov; Strømgaard, Kristian.

In: A C S Chemical Biology, Vol. 8, No. 9, 20.09.2013, p. 2033-2041.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nørager, NG, Jensen, CB, Rathje, M, Andersen, J, Madsen, KL, Kristensen, AS & Strømgaard, K 2013, 'Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons', A C S Chemical Biology, vol. 8, no. 9, pp. 2033-2041. https://doi.org/10.1021/cb400272m

APA

Nørager, N. G., Jensen, C. B., Rathje, M., Andersen, J., Madsen, K. L., Kristensen, A. S., & Strømgaard, K. (2013). Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons. A C S Chemical Biology, 8(9), 2033-2041. https://doi.org/10.1021/cb400272m

Vancouver

Nørager NG, Jensen CB, Rathje M, Andersen J, Madsen KL, Kristensen AS et al. Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons. A C S Chemical Biology. 2013 Sep 20;8(9):2033-2041. https://doi.org/10.1021/cb400272m

Author

Nørager, Niels Grøn ; Jensen, Christel Barker ; Rathje, Mette ; Andersen, Jacob ; Madsen, Kenneth Lindegaard ; Kristensen, Anders Skov ; Strømgaard, Kristian. / Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons. In: A C S Chemical Biology. 2013 ; Vol. 8, No. 9. pp. 2033-2041.

Bibtex

@article{5cdb9a80aa184aa08f8fc4095018eca3,
title = "Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons",
abstract = "The natural product argiotoxin-636 (ArgTX-636) found in the venom of the Argiope lobata spider is a potent open-channel blocker of ionotropic glutamate (iGlu) receptors, and recently, two analogues, ArgTX-75 and ArgTX-48, were identified with increased potency and selectivity for iGlu receptor subtypes. Here, we have exploited these analogues as templates in the development of fluorescent iGlu receptor ligands to be employed as unique tools for dynamic studies. Eighteen fluorescent analogues were designed and synthesized, and subsequently pharmacologically evaluated at three iGlu receptor subtypes, which resulted in the discovery of highly potent fluorescent iGlu receptor antagonists with IC50 values as low as 11 nM. The most promising ligands were further characterized showing retention of their mechanism of action, as open-channel blockers of iGlu receptors, as well as preservation of the photophysical properties of the incorporated fluorophores. Finally, we demonstrate the applicability of the developed probes for imaging of iGlu receptors in hippocampal neurons.",
author = "N{\o}rager, {Niels Gr{\o}n} and Jensen, {Christel Barker} and Mette Rathje and Jacob Andersen and Madsen, {Kenneth Lindegaard} and Kristensen, {Anders Skov} and Kristian Str{\o}mgaard",
year = "2013",
month = sep,
day = "20",
doi = "10.1021/cb400272m",
language = "English",
volume = "8",
pages = "2033--2041",
journal = "A C S Chemical Biology",
issn = "1554-8929",
publisher = "American Chemical Society",
number = "9",

}

RIS

TY - JOUR

T1 - Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons

AU - Nørager, Niels Grøn

AU - Jensen, Christel Barker

AU - Rathje, Mette

AU - Andersen, Jacob

AU - Madsen, Kenneth Lindegaard

AU - Kristensen, Anders Skov

AU - Strømgaard, Kristian

PY - 2013/9/20

Y1 - 2013/9/20

N2 - The natural product argiotoxin-636 (ArgTX-636) found in the venom of the Argiope lobata spider is a potent open-channel blocker of ionotropic glutamate (iGlu) receptors, and recently, two analogues, ArgTX-75 and ArgTX-48, were identified with increased potency and selectivity for iGlu receptor subtypes. Here, we have exploited these analogues as templates in the development of fluorescent iGlu receptor ligands to be employed as unique tools for dynamic studies. Eighteen fluorescent analogues were designed and synthesized, and subsequently pharmacologically evaluated at three iGlu receptor subtypes, which resulted in the discovery of highly potent fluorescent iGlu receptor antagonists with IC50 values as low as 11 nM. The most promising ligands were further characterized showing retention of their mechanism of action, as open-channel blockers of iGlu receptors, as well as preservation of the photophysical properties of the incorporated fluorophores. Finally, we demonstrate the applicability of the developed probes for imaging of iGlu receptors in hippocampal neurons.

AB - The natural product argiotoxin-636 (ArgTX-636) found in the venom of the Argiope lobata spider is a potent open-channel blocker of ionotropic glutamate (iGlu) receptors, and recently, two analogues, ArgTX-75 and ArgTX-48, were identified with increased potency and selectivity for iGlu receptor subtypes. Here, we have exploited these analogues as templates in the development of fluorescent iGlu receptor ligands to be employed as unique tools for dynamic studies. Eighteen fluorescent analogues were designed and synthesized, and subsequently pharmacologically evaluated at three iGlu receptor subtypes, which resulted in the discovery of highly potent fluorescent iGlu receptor antagonists with IC50 values as low as 11 nM. The most promising ligands were further characterized showing retention of their mechanism of action, as open-channel blockers of iGlu receptors, as well as preservation of the photophysical properties of the incorporated fluorophores. Finally, we demonstrate the applicability of the developed probes for imaging of iGlu receptors in hippocampal neurons.

U2 - 10.1021/cb400272m

DO - 10.1021/cb400272m

M3 - Journal article

C2 - 23838571

VL - 8

SP - 2033

EP - 2041

JO - A C S Chemical Biology

JF - A C S Chemical Biology

SN - 1554-8929

IS - 9

ER -

ID: 94827771