Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology

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

Standard

Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology. / Hauwert, Niels J.; Mocking, Tamara A.M.; Da Costa Pereira, Daniel; Kooistra, Albert J.; Wijnen, Lisa M.; Vreeker, Gerda C.M.; Verweij, Eléonore W.E.; De Boer, Albertus H.; Smit, Martine J.; De Graaf, Chris; Vischer, Henry F.; De Esch, Iwan J.P.; Wijtmans, Maikel; Leurs, Rob.

In: Journal of the American Chemical Society, Vol. 140, No. 12, 28.03.2018, p. 4232-4243.

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

Harvard

Hauwert, NJ, Mocking, TAM, Da Costa Pereira, D, Kooistra, AJ, Wijnen, LM, Vreeker, GCM, Verweij, EWE, De Boer, AH, Smit, MJ, De Graaf, C, Vischer, HF, De Esch, IJP, Wijtmans, M & Leurs, R 2018, 'Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology', Journal of the American Chemical Society, vol. 140, no. 12, pp. 4232-4243. https://doi.org/10.1021/jacs.7b11422

APA

Hauwert, N. J., Mocking, T. A. M., Da Costa Pereira, D., Kooistra, A. J., Wijnen, L. M., Vreeker, G. C. M., Verweij, E. W. E., De Boer, A. H., Smit, M. J., De Graaf, C., Vischer, H. F., De Esch, I. J. P., Wijtmans, M., & Leurs, R. (2018). Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology. Journal of the American Chemical Society, 140(12), 4232-4243. https://doi.org/10.1021/jacs.7b11422

Vancouver

Hauwert NJ, Mocking TAM, Da Costa Pereira D, Kooistra AJ, Wijnen LM, Vreeker GCM et al. Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology. Journal of the American Chemical Society. 2018 Mar 28;140(12):4232-4243. https://doi.org/10.1021/jacs.7b11422

Author

Hauwert, Niels J. ; Mocking, Tamara A.M. ; Da Costa Pereira, Daniel ; Kooistra, Albert J. ; Wijnen, Lisa M. ; Vreeker, Gerda C.M. ; Verweij, Eléonore W.E. ; De Boer, Albertus H. ; Smit, Martine J. ; De Graaf, Chris ; Vischer, Henry F. ; De Esch, Iwan J.P. ; Wijtmans, Maikel ; Leurs, Rob. / Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology. In: Journal of the American Chemical Society. 2018 ; Vol. 140, No. 12. pp. 4232-4243.

Bibtex

@article{2247ffea9e1044d289928671481badbc,
title = "Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology",
abstract = "Noninvasive methods to modulate G protein-coupled receptors (GPCRs) with temporal and spatial precision are in great demand. Photopharmacology uses photons to control in situ the biological properties of photoswitchable small-molecule ligands, which bodes well for chemical biological precision approaches. Integrating the light-switchable configurational properties of an azobenzene into the ligand core, we developed a bidirectional antagonist toolbox for an archetypical family A GPCR, the histamine H3 receptor (H3R). From 16 newly synthesized photoswitchable compounds, VUF14738 (28) and VUF14862 (33) were selected as they swiftly and reversibly photoisomerize and show over 10-fold increased or decreased H3R binding affinities, respectively, upon illumination at 360 nm. Both ligands combine long thermal half-lives with fast and high photochemical trans-/cis conversion, allowing their use in real-time electrophysiology experiments with oocytes to confirm dynamic photomodulation of H3R activation in repeated second-scale cycles. VUF14738 and VUF14862 are robust and fatigue-resistant photoswitchable GPCR antagonists suitable for spatiotemporal studies of H3R signaling.",
author = "Hauwert, {Niels J.} and Mocking, {Tamara A.M.} and {Da Costa Pereira}, Daniel and Kooistra, {Albert J.} and Wijnen, {Lisa M.} and Vreeker, {Gerda C.M.} and Verweij, {El{\'e}onore W.E.} and {De Boer}, {Albertus H.} and Smit, {Martine J.} and {De Graaf}, Chris and Vischer, {Henry F.} and {De Esch}, {Iwan J.P.} and Maikel Wijtmans and Rob Leurs",
year = "2018",
month = mar,
day = "28",
doi = "10.1021/jacs.7b11422",
language = "English",
volume = "140",
pages = "4232--4243",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",
number = "12",

}

RIS

TY - JOUR

T1 - Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology

AU - Hauwert, Niels J.

AU - Mocking, Tamara A.M.

AU - Da Costa Pereira, Daniel

AU - Kooistra, Albert J.

AU - Wijnen, Lisa M.

AU - Vreeker, Gerda C.M.

AU - Verweij, Eléonore W.E.

AU - De Boer, Albertus H.

AU - Smit, Martine J.

AU - De Graaf, Chris

AU - Vischer, Henry F.

AU - De Esch, Iwan J.P.

AU - Wijtmans, Maikel

AU - Leurs, Rob

PY - 2018/3/28

Y1 - 2018/3/28

N2 - Noninvasive methods to modulate G protein-coupled receptors (GPCRs) with temporal and spatial precision are in great demand. Photopharmacology uses photons to control in situ the biological properties of photoswitchable small-molecule ligands, which bodes well for chemical biological precision approaches. Integrating the light-switchable configurational properties of an azobenzene into the ligand core, we developed a bidirectional antagonist toolbox for an archetypical family A GPCR, the histamine H3 receptor (H3R). From 16 newly synthesized photoswitchable compounds, VUF14738 (28) and VUF14862 (33) were selected as they swiftly and reversibly photoisomerize and show over 10-fold increased or decreased H3R binding affinities, respectively, upon illumination at 360 nm. Both ligands combine long thermal half-lives with fast and high photochemical trans-/cis conversion, allowing their use in real-time electrophysiology experiments with oocytes to confirm dynamic photomodulation of H3R activation in repeated second-scale cycles. VUF14738 and VUF14862 are robust and fatigue-resistant photoswitchable GPCR antagonists suitable for spatiotemporal studies of H3R signaling.

AB - Noninvasive methods to modulate G protein-coupled receptors (GPCRs) with temporal and spatial precision are in great demand. Photopharmacology uses photons to control in situ the biological properties of photoswitchable small-molecule ligands, which bodes well for chemical biological precision approaches. Integrating the light-switchable configurational properties of an azobenzene into the ligand core, we developed a bidirectional antagonist toolbox for an archetypical family A GPCR, the histamine H3 receptor (H3R). From 16 newly synthesized photoswitchable compounds, VUF14738 (28) and VUF14862 (33) were selected as they swiftly and reversibly photoisomerize and show over 10-fold increased or decreased H3R binding affinities, respectively, upon illumination at 360 nm. Both ligands combine long thermal half-lives with fast and high photochemical trans-/cis conversion, allowing their use in real-time electrophysiology experiments with oocytes to confirm dynamic photomodulation of H3R activation in repeated second-scale cycles. VUF14738 and VUF14862 are robust and fatigue-resistant photoswitchable GPCR antagonists suitable for spatiotemporal studies of H3R signaling.

UR - http://www.scopus.com/inward/record.url?scp=85044672191&partnerID=8YFLogxK

U2 - 10.1021/jacs.7b11422

DO - 10.1021/jacs.7b11422

M3 - Journal article

C2 - 29470065

AN - SCOPUS:85044672191

VL - 140

SP - 4232

EP - 4243

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 12

ER -

ID: 199351450