Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist. / Andersen, Trine F; Vogensen, Stine B; Jensen, Lars S; Knapp, Kolja M; Strømgaard, Kristian.

In: Bioorganic & Medicinal Chemistry, Vol. 13, No. 17, 01.09.2005, p. 5104-5112.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Andersen, TF, Vogensen, SB, Jensen, LS, Knapp, KM & Strømgaard, K 2005, 'Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist', Bioorganic & Medicinal Chemistry, vol. 13, no. 17, pp. 5104-5112. https://doi.org/10.1016/j.bmc.2005.05.023

APA

Andersen, T. F., Vogensen, S. B., Jensen, L. S., Knapp, K. M., & Strømgaard, K. (2005). Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist. Bioorganic & Medicinal Chemistry, 13(17), 5104-5112. https://doi.org/10.1016/j.bmc.2005.05.023

Vancouver

Andersen TF, Vogensen SB, Jensen LS, Knapp KM, Strømgaard K. Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist. Bioorganic & Medicinal Chemistry. 2005 Sep 1;13(17):5104-5112. https://doi.org/10.1016/j.bmc.2005.05.023

Author

Andersen, Trine F ; Vogensen, Stine B ; Jensen, Lars S ; Knapp, Kolja M ; Strømgaard, Kristian. / Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist. In: Bioorganic & Medicinal Chemistry. 2005 ; Vol. 13, No. 17. pp. 5104-5112.

Bibtex

@article{660dc2ebbc3647c2a9bf61c523d9e47c,
title = "Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist",
abstract = "Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin-433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are used for the characterization of subtypes of ionotropic glutamate receptors, the Ca2+-permeable AMPA and kainate receptors. A derivative of the native polyamine toxin, philanthotoxin-56 (PhTX-56), has recently been shown to be an exceptionally potent and selective antagonist of Ca2+-permeable AMPA receptors. PhTX-56 and its labeled derivatives are promising tools for structure-function studies of the ion channel of the AMPA receptor. We now describe the design and synthesis of 3H-, 13C-, and 15N-labeled derivatives of PhTX-56 for molecular level studies of AMPA receptors. [3H]PhTX-56 was prepared from a diiodo-precursor with high specific radioactivity, providing the first radiolabeled ligand binding to the pore-forming part of AMPA receptors. For advanced biological NMR studies, 13C and 15N-labeled PhTX-56 were synthesized using solid-phase synthesis. These analogs can provide detailed information on the ligand-receptor interaction. In conclusion, synthesis of labeled derivatives of PhTX-56 provides important tools for future studies of the pore-forming region of AMPA receptors.",
keywords = "Animals, Chromatography, High Pressure Liquid, Drug Design, Isotopes, Magnetic Resonance Spectroscopy, Mass Spectrometry, Molecular Structure, Polyamines, Receptors, AMPA, Spectrophotometry, Ultraviolet, Tyrosine",
author = "Andersen, {Trine F} and Vogensen, {Stine B} and Jensen, {Lars S} and Knapp, {Kolja M} and Kristian Str{\o}mgaard",
year = "2005",
month = "9",
day = "1",
doi = "10.1016/j.bmc.2005.05.023",
language = "English",
volume = "13",
pages = "5104--5112",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Pergamon Press",
number = "17",

}

RIS

TY - JOUR

T1 - Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist

AU - Andersen, Trine F

AU - Vogensen, Stine B

AU - Jensen, Lars S

AU - Knapp, Kolja M

AU - Strømgaard, Kristian

PY - 2005/9/1

Y1 - 2005/9/1

N2 - Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin-433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are used for the characterization of subtypes of ionotropic glutamate receptors, the Ca2+-permeable AMPA and kainate receptors. A derivative of the native polyamine toxin, philanthotoxin-56 (PhTX-56), has recently been shown to be an exceptionally potent and selective antagonist of Ca2+-permeable AMPA receptors. PhTX-56 and its labeled derivatives are promising tools for structure-function studies of the ion channel of the AMPA receptor. We now describe the design and synthesis of 3H-, 13C-, and 15N-labeled derivatives of PhTX-56 for molecular level studies of AMPA receptors. [3H]PhTX-56 was prepared from a diiodo-precursor with high specific radioactivity, providing the first radiolabeled ligand binding to the pore-forming part of AMPA receptors. For advanced biological NMR studies, 13C and 15N-labeled PhTX-56 were synthesized using solid-phase synthesis. These analogs can provide detailed information on the ligand-receptor interaction. In conclusion, synthesis of labeled derivatives of PhTX-56 provides important tools for future studies of the pore-forming region of AMPA receptors.

AB - Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin-433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are used for the characterization of subtypes of ionotropic glutamate receptors, the Ca2+-permeable AMPA and kainate receptors. A derivative of the native polyamine toxin, philanthotoxin-56 (PhTX-56), has recently been shown to be an exceptionally potent and selective antagonist of Ca2+-permeable AMPA receptors. PhTX-56 and its labeled derivatives are promising tools for structure-function studies of the ion channel of the AMPA receptor. We now describe the design and synthesis of 3H-, 13C-, and 15N-labeled derivatives of PhTX-56 for molecular level studies of AMPA receptors. [3H]PhTX-56 was prepared from a diiodo-precursor with high specific radioactivity, providing the first radiolabeled ligand binding to the pore-forming part of AMPA receptors. For advanced biological NMR studies, 13C and 15N-labeled PhTX-56 were synthesized using solid-phase synthesis. These analogs can provide detailed information on the ligand-receptor interaction. In conclusion, synthesis of labeled derivatives of PhTX-56 provides important tools for future studies of the pore-forming region of AMPA receptors.

KW - Animals

KW - Chromatography, High Pressure Liquid

KW - Drug Design

KW - Isotopes

KW - Magnetic Resonance Spectroscopy

KW - Mass Spectrometry

KW - Molecular Structure

KW - Polyamines

KW - Receptors, AMPA

KW - Spectrophotometry, Ultraviolet

KW - Tyrosine

U2 - 10.1016/j.bmc.2005.05.023

DO - 10.1016/j.bmc.2005.05.023

M3 - Journal article

C2 - 15990320

VL - 13

SP - 5104

EP - 5112

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 17

ER -

ID: 45823975