Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1

Stefanie Kickinger; Maria E.K. Lie; Akihiro Suemasa; Anas Al-Khawaja; Koichi Fujiwara; Mizuki Watanabe; Kristine S. Wilhelmsen; Christina B. Falk-Petersen; Bente Frølund; Satoshi Shuto; Gerhard F. Ecker; Petrine Wellendorph

doi:10.3389/fchem.2021.736457

Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1

Stefanie Kickinger
, Maria E.K. Lie
, Akihiro Suemasa
, Anas Al-Khawaja
, Koichi Fujiwara
, Mizuki Watanabe
, Kristine S. Wilhelmsen
, Christina B. Falk-Petersen
, Bente Frølund
, Satoshi Shuto
, Gerhard F. Ecker
, Petrine Wellendorph

Department of Pharmaceutical Sciences

Publications: Contribution to journal › Article › Peer Reviewed

Original language	English
Article number	736457
Number of pages	13
Journal	Frontiers in Chemistry
Volume	9
DOIs	https://doi.org/10.3389/fchem.2021.736457
Publication status	Published - 14 Sept 2021

Funding

The authors would like to thank Professor Arne Schousboe for fruitful discussions. The authors thank the Drug Research Academy and the doctoral program MolTag for continued support. This research was funded by MEXT/JSPS KAKENHI Grant Numbers JP19H01014 (to SS), JP19K06965 (to MW), Takeda Science Foundation (to MW), Hørslevfonden (to ML), the Austrian Science Fund (Austrian Science Fund FWF Grant Number W1232 to SK) and partly by Platform Project for Supporting Drug Discovery and Life Science Research (BINDS) from AMED under Grant Number JP18am0101093.

Austrian Fields of Science 2012

301207 Pharmaceutical chemistry

Keywords

BGT1
bicyclo-GABA
binding mode analysis
competitive inhibition
computational chemistry
GABA transporter
molecular docking, molecular dynamics
SLC6 neurotransmitter transporters
SUBTYPE-SELECTIVE INHIBITOR
ACTIVATION
CARBON
ARYLATION
GABA TRANSPORTER
SLC6A12
molecular dynamics
IDENTIFICATION
molecular docking
DYNAMICS
MGAT2
BINDING

Access to Document

10.3389/fchem.2021.736457Licence: CC BY 4.0

https://phaidra.univie.ac.at/o:1602848Licence: CC BY 4.0

Cite this

Kickinger, S., Lie, M. E. K., Suemasa, A., Al-Khawaja, A., Fujiwara, K., Watanabe, M., Wilhelmsen, K. S., Falk-Petersen, C. B., Frølund, B., Shuto, S., Ecker, G. F., & Wellendorph, P. (2021). Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1. Frontiers in Chemistry, 9, Article 736457. https://doi.org/10.3389/fchem.2021.736457

@article{ac8c52afd0064733b8e5b19c16de815f,

title = "Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1",

keywords = "BGT1, bicyclo-GABA, binding mode analysis, competitive inhibition, computational chemistry, GABA transporter, molecular docking, molecular dynamics, SLC6 neurotransmitter transporters, SUBTYPE-SELECTIVE INHIBITOR, ACTIVATION, CARBON, ARYLATION, GABA TRANSPORTER, SLC6A12, molecular dynamics, IDENTIFICATION, molecular docking, DYNAMICS, MGAT2, BINDING",

author = "Stefanie Kickinger and Lie, \{Maria E.K.\} and Akihiro Suemasa and Anas Al-Khawaja and Koichi Fujiwara and Mizuki Watanabe and Wilhelmsen, \{Kristine S.\} and Falk-Petersen, \{Christina B.\} and Bente Fr{\o}lund and Satoshi Shuto and Ecker, \{Gerhard F.\} and Petrine Wellendorph",

note = "Funding Information: The authors would like to thank Professor Arne Schousboe for fruitful discussions. The authors thank the Drug Research Academy and the doctoral program MolTag for continued support. Funding Information: This research was funded by MEXT/JSPS KAKENHI Grant Numbers JP19H01014 (to SS), JP19K06965 (to MW), Takeda Science Foundation (to MW), H{\o}rslevfonden (to ML), the Austrian Science Fund (Austrian Science Fund FWF Grant Number W1232 to SK) and partly by Platform Project for Supporting Drug Discovery and Life Science Research (BINDS) from AMED under Grant Number JP18am0101093. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Kickinger, Lie, Suemasa, Al-Khawaja, Fujiwara, Watanabe, Wilhelmsen, Falk-Petersen, Fr{\o}lund, Shuto, Ecker and Wellendorph. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = sep,

day = "14",

doi = "10.3389/fchem.2021.736457",

language = "English",

volume = "9",

journal = "Frontiers in Chemistry",

issn = "2296-2646",

publisher = "FRONTIERS MEDIA SA",

}

Kickinger, S, Lie, MEK, Suemasa, A, Al-Khawaja, A, Fujiwara, K, Watanabe, M, Wilhelmsen, KS, Falk-Petersen, CB, Frølund, B, Shuto, S, Ecker, GF & Wellendorph, P 2021, 'Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1', Frontiers in Chemistry, vol. 9, 736457. https://doi.org/10.3389/fchem.2021.736457

TY - JOUR

T1 - Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1

AU - Kickinger, Stefanie

AU - Lie, Maria E.K.

AU - Suemasa, Akihiro

AU - Al-Khawaja, Anas

AU - Fujiwara, Koichi

AU - Watanabe, Mizuki

AU - Wilhelmsen, Kristine S.

AU - Falk-Petersen, Christina B.

AU - Frølund, Bente

AU - Shuto, Satoshi

AU - Ecker, Gerhard F.

AU - Wellendorph, Petrine

N1 - Funding Information: The authors would like to thank Professor Arne Schousboe for fruitful discussions. The authors thank the Drug Research Academy and the doctoral program MolTag for continued support. Funding Information: This research was funded by MEXT/JSPS KAKENHI Grant Numbers JP19H01014 (to SS), JP19K06965 (to MW), Takeda Science Foundation (to MW), Hørslevfonden (to ML), the Austrian Science Fund (Austrian Science Fund FWF Grant Number W1232 to SK) and partly by Platform Project for Supporting Drug Discovery and Life Science Research (BINDS) from AMED under Grant Number JP18am0101093. Publisher Copyright: © Copyright © 2021 Kickinger, Lie, Suemasa, Al-Khawaja, Fujiwara, Watanabe, Wilhelmsen, Falk-Petersen, Frølund, Shuto, Ecker and Wellendorph. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9/14

Y1 - 2021/9/14

KW - BGT1

KW - bicyclo-GABA

KW - binding mode analysis

KW - competitive inhibition

KW - computational chemistry

KW - GABA transporter

KW - molecular docking, molecular dynamics

KW - SLC6 neurotransmitter transporters

KW - SUBTYPE-SELECTIVE INHIBITOR

KW - ACTIVATION

KW - CARBON

KW - ARYLATION

KW - GABA TRANSPORTER

KW - SLC6A12

KW - molecular dynamics

KW - IDENTIFICATION

KW - molecular docking

KW - DYNAMICS

KW - MGAT2

KW - BINDING

UR - https://www.scopus.com/pages/publications/85115987395

U2 - 10.3389/fchem.2021.736457

DO - 10.3389/fchem.2021.736457

M3 - Article

AN - SCOPUS:85115987395

SN - 2296-2646

VL - 9

JO - Frontiers in Chemistry

JF - Frontiers in Chemistry

M1 - 736457

ER -

Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1

Funding

Austrian Fields of Science 2012

Keywords

Access to Document

Other files and links

Fingerprint

Molecular Drug Targets

Cite this

Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1

Funding

Austrian Fields of Science 2012

Keywords

Access to Document

Other files and links

Fingerprint

Projects

Molecular Drug Targets

Cite this