Structure-based discovery of novel US28 small molecule ligands with different modes of action

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Structure-based discovery of novel US28 small molecule ligands with different modes of action. / Lückmann, Michael; Amarandi, Roxana-Maria; Papargyri, Natalia; Jakobsen, Mette H; Christiansen, Elisabeth; Jensen, Lars Juhl; Pui, Aurel; Schwartz, Thue W.; Rosenkilde, Mette Marie; Frimurer, Thomas Michael.

In: Chemical Biology & Drug Design, Vol. 89, No. 3, 2017, p. 289–296.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lückmann, M, Amarandi, R-M, Papargyri, N, Jakobsen, MH, Christiansen, E, Jensen, LJ, Pui, A, Schwartz, TW, Rosenkilde, MM & Frimurer, TM 2017, 'Structure-based discovery of novel US28 small molecule ligands with different modes of action', Chemical Biology & Drug Design, vol. 89, no. 3, pp. 289–296. https://doi.org/10.1111/cbdd.12848

APA

Lückmann, M., Amarandi, R-M., Papargyri, N., Jakobsen, M. H., Christiansen, E., Jensen, L. J., ... Frimurer, T. M. (2017). Structure-based discovery of novel US28 small molecule ligands with different modes of action. Chemical Biology & Drug Design, 89(3), 289–296. https://doi.org/10.1111/cbdd.12848

Vancouver

Lückmann M, Amarandi R-M, Papargyri N, Jakobsen MH, Christiansen E, Jensen LJ et al. Structure-based discovery of novel US28 small molecule ligands with different modes of action. Chemical Biology & Drug Design. 2017;89(3):289–296. https://doi.org/10.1111/cbdd.12848

Author

Lückmann, Michael ; Amarandi, Roxana-Maria ; Papargyri, Natalia ; Jakobsen, Mette H ; Christiansen, Elisabeth ; Jensen, Lars Juhl ; Pui, Aurel ; Schwartz, Thue W. ; Rosenkilde, Mette Marie ; Frimurer, Thomas Michael. / Structure-based discovery of novel US28 small molecule ligands with different modes of action. In: Chemical Biology & Drug Design. 2017 ; Vol. 89, No. 3. pp. 289–296.

Bibtex

@article{c47cc6ea725a4639ac144bed8f326833,
title = "Structure-based discovery of novel US28 small molecule ligands with different modes of action",
abstract = "The human cytomegalovirus-encoded G protein-coupled receptor US28 is a constitutively active receptor, which can recognize various chemokines. Despite the recent determination of its 2.9 {\AA} crystal structure, potent and US28-specific tool compounds are still scarce. Here, we used structural information from a refined US28:VUF2274 complex for virtual screening of >12 million commercially available small molecule compounds. Using a combined receptor- and ligand-based approach, we tested 98 of the top 0.1{\%} ranked compounds, revealing novel chemotypes as compared to the ~1.45 million known ligands in the ChEMBL database. Two compounds were confirmed as agonist and inverse agonist, respectively, in both IP accumulation and Ca(2+) mobilization assays. The screening setup presented in this work is computationally inexpensive and therefore particularly useful in an academic setting as it enables simultaneous testing in binding as well as in different functional assays and/or species without actual chemical synthesis.",
author = "Michael L{\"u}ckmann and Roxana-Maria Amarandi and Natalia Papargyri and Jakobsen, {Mette H} and Elisabeth Christiansen and Jensen, {Lars Juhl} and Aurel Pui and Schwartz, {Thue W.} and Rosenkilde, {Mette Marie} and Frimurer, {Thomas Michael}",
note = "{\circledC} 2016 John Wiley & Sons A/S.",
year = "2017",
doi = "10.1111/cbdd.12848",
language = "English",
volume = "89",
pages = "289–296",
journal = "Chemical Biology and Drug Design (Print)",
issn = "1747-0277",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Structure-based discovery of novel US28 small molecule ligands with different modes of action

AU - Lückmann, Michael

AU - Amarandi, Roxana-Maria

AU - Papargyri, Natalia

AU - Jakobsen, Mette H

AU - Christiansen, Elisabeth

AU - Jensen, Lars Juhl

AU - Pui, Aurel

AU - Schwartz, Thue W.

AU - Rosenkilde, Mette Marie

AU - Frimurer, Thomas Michael

N1 - © 2016 John Wiley & Sons A/S.

PY - 2017

Y1 - 2017

N2 - The human cytomegalovirus-encoded G protein-coupled receptor US28 is a constitutively active receptor, which can recognize various chemokines. Despite the recent determination of its 2.9 Å crystal structure, potent and US28-specific tool compounds are still scarce. Here, we used structural information from a refined US28:VUF2274 complex for virtual screening of >12 million commercially available small molecule compounds. Using a combined receptor- and ligand-based approach, we tested 98 of the top 0.1% ranked compounds, revealing novel chemotypes as compared to the ~1.45 million known ligands in the ChEMBL database. Two compounds were confirmed as agonist and inverse agonist, respectively, in both IP accumulation and Ca(2+) mobilization assays. The screening setup presented in this work is computationally inexpensive and therefore particularly useful in an academic setting as it enables simultaneous testing in binding as well as in different functional assays and/or species without actual chemical synthesis.

AB - The human cytomegalovirus-encoded G protein-coupled receptor US28 is a constitutively active receptor, which can recognize various chemokines. Despite the recent determination of its 2.9 Å crystal structure, potent and US28-specific tool compounds are still scarce. Here, we used structural information from a refined US28:VUF2274 complex for virtual screening of >12 million commercially available small molecule compounds. Using a combined receptor- and ligand-based approach, we tested 98 of the top 0.1% ranked compounds, revealing novel chemotypes as compared to the ~1.45 million known ligands in the ChEMBL database. Two compounds were confirmed as agonist and inverse agonist, respectively, in both IP accumulation and Ca(2+) mobilization assays. The screening setup presented in this work is computationally inexpensive and therefore particularly useful in an academic setting as it enables simultaneous testing in binding as well as in different functional assays and/or species without actual chemical synthesis.

U2 - 10.1111/cbdd.12848

DO - 10.1111/cbdd.12848

M3 - Journal article

VL - 89

SP - 289

EP - 296

JO - Chemical Biology and Drug Design (Print)

JF - Chemical Biology and Drug Design (Print)

SN - 1747-0277

IS - 3

ER -

ID: 166506941