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

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

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.

I: Journal of Medicinal Chemistry, Bind 53, Nr. 20, 2010, s. 7441-7451.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

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, bind 53, nr. 20, s. 7441-7451. https://doi.org/10.1021/jm100886h

APA

Frølund, S., Bella, A., Kristensen, A. S., Ziegler, H. L., Witt, M., Olsen, C. A., Strømgaard, K., Franzyk, H., & 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 o.a. 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. I: Journal of Medicinal Chemistry. 2010 ; Bind 53, Nr. 20. s. 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