Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions

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Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions. / Bach, Anders*; Pedersen, Søren W.; Dorr, Liam A.; Vallon, Gary; Ripoche, Isabelle; Ducki, Sylvie; Lian, Lu-Yun* (*Corresponding).

In: Scientific Reports, Vol. 5, 12157, 2015, p. 1-12.

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

Harvard

Bach, Anders*; Pedersen, Søren W.; Dorr, Liam A.; Vallon, Gary; Ripoche, Isabelle; Ducki, Sylvie; Lian, Lu-Yun* (*Corresponding) 2015, 'Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions', Scientific Reports, vol. 5, 12157, pp. 1-12. https://doi.org/10.1038/srep12157

APA

Bach, Anders*; Pedersen, Søren W.; Dorr, Liam A.; Vallon, Gary; Ripoche, Isabelle; Ducki, Sylvie; Lian, Lu-Yun* (*Corresponding) (2015). Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions. Scientific Reports, 5, 1-12. [12157]. https://doi.org/10.1038/srep12157

Vancouver

Bach, Anders*; Pedersen, Søren W.; Dorr, Liam A.; Vallon, Gary; Ripoche, Isabelle; Ducki, Sylvie; Lian, Lu-Yun* (*Corresponding). Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions. Scientific Reports. 2015;5:1-12. 12157. https://doi.org/10.1038/srep12157

Author

Bach, Anders*; Pedersen, Søren W.; Dorr, Liam A.; Vallon, Gary; Ripoche, Isabelle; Ducki, Sylvie; Lian, Lu-Yun* (*Corresponding). / Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions. In: Scientific Reports. 2015 ; Vol. 5. pp. 1-12.

Bibtex

@article{86aac64ee37f4bce8ebd659a81867f72,
title = "Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions",
abstract = "ZL006 and IC87201 have been presented as efficient inhibitors of the nNOS/PSD-95 protein-protein interaction and shown great promise in cellular experiments and animal models of ischemic stroke and pain. Here, we investigate the proposed mechanism of action of ZL006 and IC87201 using biochemical and biophysical methods, such as fluorescence polarization (FP), isothermal titration calorimetry (ITC), and (1)H-(15)N HSQC NMR. Our data show that under the applied in vitro conditions, ZL006 and IC87201 do not interact with the PDZ domains of nNOS or PSD-95, nor inhibit the nNOS-PDZ/PSD-95-PDZ interface by interacting with the β-finger of nNOS-PDZ. Our findings have implications for further medicinal chemistry efforts of ZL006, IC87201 and analogues, and challenge the general and widespread view on their mechanism of action.",
author = "Anders Bach and {Bach, Anders*; Pedersen, S{\o}ren W.; Dorr, Liam A.; Vallon, Gary; Ripoche, Isabelle; Ducki, Sylvie; Lian, Lu-Yun* (*Corresponding)}",
year = "2015",
doi = "10.1038/srep12157",
language = "English",
volume = "5",
pages = "1--12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions

AU - Bach, Anders

AU - Bach, Anders; Pedersen, Søren W.; Dorr, Liam A.; Vallon, Gary; Ripoche, Isabelle; Ducki, Sylvie; Lian, Lu-Yun (Corresponding)

PY - 2015

Y1 - 2015

N2 - ZL006 and IC87201 have been presented as efficient inhibitors of the nNOS/PSD-95 protein-protein interaction and shown great promise in cellular experiments and animal models of ischemic stroke and pain. Here, we investigate the proposed mechanism of action of ZL006 and IC87201 using biochemical and biophysical methods, such as fluorescence polarization (FP), isothermal titration calorimetry (ITC), and (1)H-(15)N HSQC NMR. Our data show that under the applied in vitro conditions, ZL006 and IC87201 do not interact with the PDZ domains of nNOS or PSD-95, nor inhibit the nNOS-PDZ/PSD-95-PDZ interface by interacting with the β-finger of nNOS-PDZ. Our findings have implications for further medicinal chemistry efforts of ZL006, IC87201 and analogues, and challenge the general and widespread view on their mechanism of action.

AB - ZL006 and IC87201 have been presented as efficient inhibitors of the nNOS/PSD-95 protein-protein interaction and shown great promise in cellular experiments and animal models of ischemic stroke and pain. Here, we investigate the proposed mechanism of action of ZL006 and IC87201 using biochemical and biophysical methods, such as fluorescence polarization (FP), isothermal titration calorimetry (ITC), and (1)H-(15)N HSQC NMR. Our data show that under the applied in vitro conditions, ZL006 and IC87201 do not interact with the PDZ domains of nNOS or PSD-95, nor inhibit the nNOS-PDZ/PSD-95-PDZ interface by interacting with the β-finger of nNOS-PDZ. Our findings have implications for further medicinal chemistry efforts of ZL006, IC87201 and analogues, and challenge the general and widespread view on their mechanism of action.

U2 - 10.1038/srep12157

DO - 10.1038/srep12157

M3 - Journal article

VL - 5

SP - 1

EP - 12

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 12157

ER -

ID: 141733202