Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: Discovery of nanomolar, nonselective, and use-dependent antagonists

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes : Discovery of nanomolar, nonselective, and use-dependent antagonists. / Frølund, Sidsel; Bella, Angelo; Kristensen, Anders Skov; Ziegler, Hanne Lindvig; Witt, Matthias; Olsen, Christian Adam; Strømgaard, Kristian; Franzyk, Henrik; Jaroszewski, Jerzy W.

In: Journal of Medicinal Chemistry, Vol. 53, No. 20, 2010, p. 7441-7451.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Frølund, S, Bella, A, Kristensen, AS, Ziegler, HL, Witt, M, Olsen, CA, Strømgaard, K, Franzyk, H & Jaroszewski, JW 2010, 'Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: Discovery of nanomolar, nonselective, and use-dependent antagonists', Journal of Medicinal Chemistry, vol. 53, no. 20, pp. 7441-7451. https://doi.org/10.1021/jm100886h

APA

Frølund, S., Bella, A., Kristensen, A. S., Ziegler, H. L., Witt, M., Olsen, C. A., ... Jaroszewski, J. W. (2010). Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: Discovery of nanomolar, nonselective, and use-dependent antagonists. Journal of Medicinal Chemistry, 53(20), 7441-7451. https://doi.org/10.1021/jm100886h

Vancouver

Frølund S, Bella A, Kristensen AS, Ziegler HL, Witt M, Olsen CA et al. Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: Discovery of nanomolar, nonselective, and use-dependent antagonists. Journal of Medicinal Chemistry. 2010;53(20):7441-7451. https://doi.org/10.1021/jm100886h

Author

Frølund, Sidsel ; Bella, Angelo ; Kristensen, Anders Skov ; Ziegler, Hanne Lindvig ; Witt, Matthias ; Olsen, Christian Adam ; Strømgaard, Kristian ; Franzyk, Henrik ; Jaroszewski, Jerzy W. / Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes : Discovery of nanomolar, nonselective, and use-dependent antagonists. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 20. pp. 7441-7451.

Bibtex

@article{0d3c89b0d07011df825b000ea68e967b,
title = "Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: Discovery of nanomolar, nonselective, and use-dependent antagonists",
abstract = "An array of analogues of the wasp toxin philanthotoxin-433, in which the asymmetric polyamine moiety was exchanged for spermine and the headgroup replaced with a variety of structurally diverse moieties, was prepared using parallel solid-phase synthesis approaches. In three analogues, the spermine moiety was extended with an amino acid tail, six compounds contained an N-acylated cyclohexylalanine, and four analogues were based on a novel diamino acid design with systematically changed spacer length between N-cyclohexylcarbonyl and N-phenylacetyl substituents. The analogues were studied using two-electrode voltage-clamp electrophysiology employing Xenopus laevis oocytes expressing GluA1(i) AMPA or GluN1/2A NMDA receptors. Several of the analogues showed significantly increased inhibition of the GluN1/2A NMDA receptor. Thus, an analogue containing N-(1-naphtyl)acetyl group showed an IC(50) value of 47 nM. For the diamino acid-based analogues, the optimal spacer length between two N-acyl groups was determined, resulting in an analogue with an IC(50) value of 106 nM.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Sidsel Fr{\o}lund and Angelo Bella and Kristensen, {Anders Skov} and Ziegler, {Hanne Lindvig} and Matthias Witt and Olsen, {Christian Adam} and Kristian Str{\o}mgaard and Henrik Franzyk and Jaroszewski, {Jerzy W}",
year = "2010",
doi = "10.1021/jm100886h",
language = "English",
volume = "53",
pages = "7441--7451",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "20",

}

RIS

TY - JOUR

T1 - Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes

T2 - Discovery of nanomolar, nonselective, and use-dependent antagonists

AU - Frølund, Sidsel

AU - Bella, Angelo

AU - Kristensen, Anders Skov

AU - Ziegler, Hanne Lindvig

AU - Witt, Matthias

AU - Olsen, Christian Adam

AU - Strømgaard, Kristian

AU - Franzyk, Henrik

AU - Jaroszewski, Jerzy W

PY - 2010

Y1 - 2010

N2 - An array of analogues of the wasp toxin philanthotoxin-433, in which the asymmetric polyamine moiety was exchanged for spermine and the headgroup replaced with a variety of structurally diverse moieties, was prepared using parallel solid-phase synthesis approaches. In three analogues, the spermine moiety was extended with an amino acid tail, six compounds contained an N-acylated cyclohexylalanine, and four analogues were based on a novel diamino acid design with systematically changed spacer length between N-cyclohexylcarbonyl and N-phenylacetyl substituents. The analogues were studied using two-electrode voltage-clamp electrophysiology employing Xenopus laevis oocytes expressing GluA1(i) AMPA or GluN1/2A NMDA receptors. Several of the analogues showed significantly increased inhibition of the GluN1/2A NMDA receptor. Thus, an analogue containing N-(1-naphtyl)acetyl group showed an IC(50) value of 47 nM. For the diamino acid-based analogues, the optimal spacer length between two N-acyl groups was determined, resulting in an analogue with an IC(50) value of 106 nM.

AB - An array of analogues of the wasp toxin philanthotoxin-433, in which the asymmetric polyamine moiety was exchanged for spermine and the headgroup replaced with a variety of structurally diverse moieties, was prepared using parallel solid-phase synthesis approaches. In three analogues, the spermine moiety was extended with an amino acid tail, six compounds contained an N-acylated cyclohexylalanine, and four analogues were based on a novel diamino acid design with systematically changed spacer length between N-cyclohexylcarbonyl and N-phenylacetyl substituents. The analogues were studied using two-electrode voltage-clamp electrophysiology employing Xenopus laevis oocytes expressing GluA1(i) AMPA or GluN1/2A NMDA receptors. Several of the analogues showed significantly increased inhibition of the GluN1/2A NMDA receptor. Thus, an analogue containing N-(1-naphtyl)acetyl group showed an IC(50) value of 47 nM. For the diamino acid-based analogues, the optimal spacer length between two N-acyl groups was determined, resulting in an analogue with an IC(50) value of 106 nM.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jm100886h

DO - 10.1021/jm100886h

M3 - Journal article

C2 - 20873775

VL - 53

SP - 7441

EP - 7451

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 20

ER -

ID: 22360245