mGluR5: Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery

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

Standard

mGluR5 : Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery. / Mølck, Christina; Harpsøe, Kasper; Gloriam, David E; Mathiesen, Jesper M; Nielsen, Søren M; Bräuner-Osborne, Hans.

In: Neurochemical Research, Vol. 39, No. 10, 10.2014, p. 1862-1875.

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

Harvard

Mølck, C, Harpsøe, K, Gloriam, DE, Mathiesen, JM, Nielsen, SM & Bräuner-Osborne, H 2014, 'mGluR5: Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery', Neurochemical Research, vol. 39, no. 10, pp. 1862-1875. https://doi.org/10.1007/s11064-014-1248-8

APA

Mølck, C., Harpsøe, K., Gloriam, D. E., Mathiesen, J. M., Nielsen, S. M., & Bräuner-Osborne, H. (2014). mGluR5: Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery. Neurochemical Research, 39(10), 1862-1875. https://doi.org/10.1007/s11064-014-1248-8

Vancouver

Mølck C, Harpsøe K, Gloriam DE, Mathiesen JM, Nielsen SM, Bräuner-Osborne H. mGluR5: Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery. Neurochemical Research. 2014 Oct;39(10):1862-1875. https://doi.org/10.1007/s11064-014-1248-8

Author

Mølck, Christina ; Harpsøe, Kasper ; Gloriam, David E ; Mathiesen, Jesper M ; Nielsen, Søren M ; Bräuner-Osborne, Hans. / mGluR5 : Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery. In: Neurochemical Research. 2014 ; Vol. 39, No. 10. pp. 1862-1875.

Bibtex

@article{416da1ff95bc4a6bbc0ae2ff1c72b611,
title = "mGluR5: Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery",
abstract = "Since its discovery in 1992, mGluR5 has attracted significant attention and been linked to several neurological and psychiatric diseases. Ligand development was initially focused on the orthosteric binding pocket, but lack of subtype selective ligands changed the focus to the transmembrane allosteric binding pocket. This strategy has resulted in several drug candidates in clinical testing. In the present article we explore the orthosteric and allosteric binding pockets in terms of structure and ligand recognition across the mGluR subtypes and groups, and discuss the clinical potential of ligands targeting these pockets. We have performed binding mode analyses of non- and group-selective orthosteric ligands based on molecular docking in mGluR crystal structures and models. For the analysis of the allosteric binding pocket we have combined data from all mGluR5-mutagenesis studies, collectively reporting five negative allosteric modulators and 47 unique mutations, and compared it to the closest related homolog, mGluR1.",
author = "Christina M{\o}lck and Kasper Harps{\o}e and Gloriam, {David E} and Mathiesen, {Jesper M} and Nielsen, {S{\o}ren M} and Hans Br{\"a}uner-Osborne",
year = "2014",
month = oct,
doi = "10.1007/s11064-014-1248-8",
language = "English",
volume = "39",
pages = "1862--1875",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer",
number = "10",

}

RIS

TY - JOUR

T1 - mGluR5

T2 - Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery

AU - Mølck, Christina

AU - Harpsøe, Kasper

AU - Gloriam, David E

AU - Mathiesen, Jesper M

AU - Nielsen, Søren M

AU - Bräuner-Osborne, Hans

PY - 2014/10

Y1 - 2014/10

N2 - Since its discovery in 1992, mGluR5 has attracted significant attention and been linked to several neurological and psychiatric diseases. Ligand development was initially focused on the orthosteric binding pocket, but lack of subtype selective ligands changed the focus to the transmembrane allosteric binding pocket. This strategy has resulted in several drug candidates in clinical testing. In the present article we explore the orthosteric and allosteric binding pockets in terms of structure and ligand recognition across the mGluR subtypes and groups, and discuss the clinical potential of ligands targeting these pockets. We have performed binding mode analyses of non- and group-selective orthosteric ligands based on molecular docking in mGluR crystal structures and models. For the analysis of the allosteric binding pocket we have combined data from all mGluR5-mutagenesis studies, collectively reporting five negative allosteric modulators and 47 unique mutations, and compared it to the closest related homolog, mGluR1.

AB - Since its discovery in 1992, mGluR5 has attracted significant attention and been linked to several neurological and psychiatric diseases. Ligand development was initially focused on the orthosteric binding pocket, but lack of subtype selective ligands changed the focus to the transmembrane allosteric binding pocket. This strategy has resulted in several drug candidates in clinical testing. In the present article we explore the orthosteric and allosteric binding pockets in terms of structure and ligand recognition across the mGluR subtypes and groups, and discuss the clinical potential of ligands targeting these pockets. We have performed binding mode analyses of non- and group-selective orthosteric ligands based on molecular docking in mGluR crystal structures and models. For the analysis of the allosteric binding pocket we have combined data from all mGluR5-mutagenesis studies, collectively reporting five negative allosteric modulators and 47 unique mutations, and compared it to the closest related homolog, mGluR1.

U2 - 10.1007/s11064-014-1248-8

DO - 10.1007/s11064-014-1248-8

M3 - Journal article

C2 - 24493625

VL - 39

SP - 1862

EP - 1875

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 10

ER -

ID: 119576998