Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**

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

Standard

Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**. / Bolding, Julie E.; Nielsen, Alexander L.; Jensen, Iben; Hansen, Tobias N.; Ryberg, Line A.; Jameson, Samuel T.; Harris, Pernille; Peters, Günther H.J.; Denu, John M.; Rogers, Joseph M.; Olsen, Christian A.

In: Angewandte Chemie - International Edition, Vol. 62, No. 49, e202314597, 2023.

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

Harvard

Bolding, JE, Nielsen, AL, Jensen, I, Hansen, TN, Ryberg, LA, Jameson, ST, Harris, P, Peters, GHJ, Denu, JM, Rogers, JM & Olsen, CA 2023, 'Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**', Angewandte Chemie - International Edition, vol. 62, no. 49, e202314597. https://doi.org/10.1002/anie.202314597

APA

Bolding, J. E., Nielsen, A. L., Jensen, I., Hansen, T. N., Ryberg, L. A., Jameson, S. T., Harris, P., Peters, G. H. J., Denu, J. M., Rogers, J. M., & Olsen, C. A. (2023). Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**. Angewandte Chemie - International Edition, 62(49), [e202314597]. https://doi.org/10.1002/anie.202314597

Vancouver

Bolding JE, Nielsen AL, Jensen I, Hansen TN, Ryberg LA, Jameson ST et al. Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**. Angewandte Chemie - International Edition. 2023;62(49). e202314597. https://doi.org/10.1002/anie.202314597

Author

Bolding, Julie E. ; Nielsen, Alexander L. ; Jensen, Iben ; Hansen, Tobias N. ; Ryberg, Line A. ; Jameson, Samuel T. ; Harris, Pernille ; Peters, Günther H.J. ; Denu, John M. ; Rogers, Joseph M. ; Olsen, Christian A. / Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**. In: Angewandte Chemie - International Edition. 2023 ; Vol. 62, No. 49.

Bibtex

@article{ff41da59f3f94ac0a2d7bb1e63da65a2,
title = "Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**",
abstract = "The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1–7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity. Here we expressed SIRT7 and, using small-angle X-ray scattering, reveal SIRT7 to be a monomeric enzyme with a low degree of globular flexibility in solution. We developed a fluorogenic assay for investigation of the substrate preferences of SIRT7 and to evaluate compounds that modulate its activity. We report several mechanism-based SIRT7 inhibitors as well as de novo cyclic peptide inhibitors selected from mRNA-display library screening that exhibit selectivity for SIRT7 over other sirtuin isoforms, stabilize SIRT7 in cells, and cause an increase in the acetylation of H3 K18.",
keywords = "Epigenetics, Histones, Lysine acylation, mRNA Display, Posttranslational Modification",
author = "Bolding, {Julie E.} and Nielsen, {Alexander L.} and Iben Jensen and Hansen, {Tobias N.} and Ryberg, {Line A.} and Jameson, {Samuel T.} and Pernille Harris and Peters, {G{\"u}nther H.J.} and Denu, {John M.} and Rogers, {Joseph M.} and Olsen, {Christian A.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",
year = "2023",
doi = "10.1002/anie.202314597",
language = "English",
volume = "62",
journal = "Angewandte Chemie International Edition",
issn = "1433-7851",
publisher = "Wiley-VCH Verlag GmbH & Co. KGaA",
number = "49",

}

RIS

TY - JOUR

T1 - Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**

AU - Bolding, Julie E.

AU - Nielsen, Alexander L.

AU - Jensen, Iben

AU - Hansen, Tobias N.

AU - Ryberg, Line A.

AU - Jameson, Samuel T.

AU - Harris, Pernille

AU - Peters, Günther H.J.

AU - Denu, John M.

AU - Rogers, Joseph M.

AU - Olsen, Christian A.

N1 - Publisher Copyright: © 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

PY - 2023

Y1 - 2023

N2 - The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1–7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity. Here we expressed SIRT7 and, using small-angle X-ray scattering, reveal SIRT7 to be a monomeric enzyme with a low degree of globular flexibility in solution. We developed a fluorogenic assay for investigation of the substrate preferences of SIRT7 and to evaluate compounds that modulate its activity. We report several mechanism-based SIRT7 inhibitors as well as de novo cyclic peptide inhibitors selected from mRNA-display library screening that exhibit selectivity for SIRT7 over other sirtuin isoforms, stabilize SIRT7 in cells, and cause an increase in the acetylation of H3 K18.

AB - The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1–7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity. Here we expressed SIRT7 and, using small-angle X-ray scattering, reveal SIRT7 to be a monomeric enzyme with a low degree of globular flexibility in solution. We developed a fluorogenic assay for investigation of the substrate preferences of SIRT7 and to evaluate compounds that modulate its activity. We report several mechanism-based SIRT7 inhibitors as well as de novo cyclic peptide inhibitors selected from mRNA-display library screening that exhibit selectivity for SIRT7 over other sirtuin isoforms, stabilize SIRT7 in cells, and cause an increase in the acetylation of H3 K18.

KW - Epigenetics

KW - Histones

KW - Lysine acylation

KW - mRNA Display

KW - Posttranslational Modification

U2 - 10.1002/anie.202314597

DO - 10.1002/anie.202314597

M3 - Journal article

C2 - 37873919

AN - SCOPUS:85175817167

VL - 62

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

SN - 1433-7851

IS - 49

M1 - e202314597

ER -

ID: 373616802