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Identification of novel GPR17-agonists by structural bioinformatics and signaling activation

Tutkimustuotosvertaisarvioitu

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Identification of novel GPR17-agonists by structural bioinformatics and signaling activation. / Saravanan, KM; Palanivel, Suresh; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram.

julkaisussa: International Journal of Biological Macromolecules, Vuosikerta 106, 2018, s. 901-907.

Tutkimustuotosvertaisarvioitu

Harvard

Saravanan, KM, Palanivel, S, Yli-Harja, O & Kandhavelu, M 2018, 'Identification of novel GPR17-agonists by structural bioinformatics and signaling activation', International Journal of Biological Macromolecules, Vuosikerta. 106, Sivut 901-907. https://doi.org/10.1016/j.ijbiomac.2017.08.088

APA

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Author

Saravanan, KM ; Palanivel, Suresh ; Yli-Harja, Olli ; Kandhavelu, Meenakshisundaram. / Identification of novel GPR17-agonists by structural bioinformatics and signaling activation. Julkaisussa: International Journal of Biological Macromolecules. 2018 ; Vuosikerta 106. Sivut 901-907.

Bibtex - Lataa

@article{cd30f23be4be4d6697c4be67e42c4ff6,
title = "Identification of novel GPR17-agonists by structural bioinformatics and signaling activation",
abstract = "G Protein-coupled Receptor 17 (GPR17) is phylogenetically related to the purinergic receptors emerged as a potential drug target for multiple sclerosis, Parkinson disease, Alzheimer disease and cancer. Unfortunately, the crystal structure of GPR17 is unresolved. With the interest in structure-based ligand discovery, we modeled the structure of GPR17. The model allowed us to identify two novel agonists, AC1MLNKK and T0510.3657 that selectively activate GPR17 which exhibit better interaction properties than previously known ligand, MDL29951. We report detailed protein-ligand interactions and the dynamics of GPR17-ligand interaction by molecular docking and molecular dynamics experiments. Ex vivo validation of GPR17-ligand interaction provides evidence that ligand T0510-3657 and AC1MLNKK inhibits the cAMP levels in GPR17-HEK293T cells, with a pEC50 of 4.79 and 4.64, respectively. In silico and ex vivo validation experiments provided the deep understanding of ligand binding with GPR17 and the present findings reported here may lead to use these two compounds as a potential activator of GPR17 for therapeutic intervention.",
author = "KM Saravanan and Suresh Palanivel and Olli Yli-Harja and Meenakshisundaram Kandhavelu",
year = "2018",
doi = "10.1016/j.ijbiomac.2017.08.088",
language = "English",
volume = "106",
pages = "901--907",
journal = "International Journal of Biological Macromolecules",
issn = "0141-8130",
publisher = "Elsevier",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Identification of novel GPR17-agonists by structural bioinformatics and signaling activation

AU - Saravanan, KM

AU - Palanivel, Suresh

AU - Yli-Harja, Olli

AU - Kandhavelu, Meenakshisundaram

PY - 2018

Y1 - 2018

N2 - G Protein-coupled Receptor 17 (GPR17) is phylogenetically related to the purinergic receptors emerged as a potential drug target for multiple sclerosis, Parkinson disease, Alzheimer disease and cancer. Unfortunately, the crystal structure of GPR17 is unresolved. With the interest in structure-based ligand discovery, we modeled the structure of GPR17. The model allowed us to identify two novel agonists, AC1MLNKK and T0510.3657 that selectively activate GPR17 which exhibit better interaction properties than previously known ligand, MDL29951. We report detailed protein-ligand interactions and the dynamics of GPR17-ligand interaction by molecular docking and molecular dynamics experiments. Ex vivo validation of GPR17-ligand interaction provides evidence that ligand T0510-3657 and AC1MLNKK inhibits the cAMP levels in GPR17-HEK293T cells, with a pEC50 of 4.79 and 4.64, respectively. In silico and ex vivo validation experiments provided the deep understanding of ligand binding with GPR17 and the present findings reported here may lead to use these two compounds as a potential activator of GPR17 for therapeutic intervention.

AB - G Protein-coupled Receptor 17 (GPR17) is phylogenetically related to the purinergic receptors emerged as a potential drug target for multiple sclerosis, Parkinson disease, Alzheimer disease and cancer. Unfortunately, the crystal structure of GPR17 is unresolved. With the interest in structure-based ligand discovery, we modeled the structure of GPR17. The model allowed us to identify two novel agonists, AC1MLNKK and T0510.3657 that selectively activate GPR17 which exhibit better interaction properties than previously known ligand, MDL29951. We report detailed protein-ligand interactions and the dynamics of GPR17-ligand interaction by molecular docking and molecular dynamics experiments. Ex vivo validation of GPR17-ligand interaction provides evidence that ligand T0510-3657 and AC1MLNKK inhibits the cAMP levels in GPR17-HEK293T cells, with a pEC50 of 4.79 and 4.64, respectively. In silico and ex vivo validation experiments provided the deep understanding of ligand binding with GPR17 and the present findings reported here may lead to use these two compounds as a potential activator of GPR17 for therapeutic intervention.

U2 - 10.1016/j.ijbiomac.2017.08.088

DO - 10.1016/j.ijbiomac.2017.08.088

M3 - Article

VL - 106

SP - 901

EP - 907

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

SN - 0141-8130

ER -