Mechanism-based inhibitors of SIRT2: structure–activity relationship, X-ray structures, target engagement, regulation of α-tubulin acetylation and inhibition of breast cancer cell migration

Autor: Alexander L. Nielsen, Andreas Stahl Madsen, Nima Rajabi, Kathrine Lundø, Minoru Yoshida, Norio Kudo, Michael Bæk, Christian A. Olsen, Carlos Moreno-Yruela, Alessia Lucidi, Martin Fontenas

Publikováno v: Nielsen, A L, Rajabi, N, Kudo, N, Lundø, K, Moreno-Yruela, C, Bæk, M, Fontenas, M, Lucidi, A, Madsen, A S, Yoshida, M & Olsen, C A 2021, ' Mechanism-based inhibitors of SIRT2: structure–activity relationship, X-ray structures, target engagement, regulation of α-tubulin acetylation and inhibition of breast cancer cell migration ', RSC Chemical Biology, vol. 2, pp. 612-626 . https://doi.org/10.1039/D0CB00036A
RSC Chemical Biology

Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. It affects diverse biological functions in the cell and has been considered a drug target in r

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5286e36b7d84447506d7380fe9a23ce3
https://doi.org/10.1101/2020.03.20.000380

Metabolic control by sirtuins and other enzymes that sense NAD+, NADH, or their ratio

Autor: Christian A. Olsen, Kristin A. Anderson, Andreas Stahl Madsen, Matthew D. Hirschey

Publikováno v: Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1858:991-998

NAD+ is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD+, NADH, and the NAD+/NADH ratio have long be

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a60666a255cbebd6dfaf37dc6e8eb0cc
https://doi.org/10.1016/j.bbabio.2017.09.005

Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities

Autor: Andreas Stahl Madsen, Ana Colaço, Alex Maolanon, Betül Kitir, Christian A. Olsen, Peter Fristrup, Ragnhild Gaard Ohm

Publikováno v: Biochemistry. 56:5134-5146

Histone deacetylases (HDACs) are validated targets for treatment of certain cancer types and play numerous regulatory roles in biology, ranging from epigenetics to metabolism. Small molecules are highly important as tool compounds for probing these m

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0d21bfb2620ab1c1e0574cfb87e6c8f
https://doi.org/10.1021/acs.biochem.7b00725

Innovative Strategies for Selective Inhibition of Histone Deacetylases

Autor: Andreas Stahl Madsen, Christian A. Olsen, Alex Maolanon

Publikováno v: Cell Chemical Biology. 23:759-768

Histone deacetylases (HDAC) are a family of closely related enzymes involved in epigenetic and posttranscriptional regulation of numerous genes and proteins. Their deregulation is associated with a number of diseases, and a handful of HDAC inhibitors

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21ab8ebdb8528a0e6f0c70f73f8f1ad1
https://doi.org/10.1016/j.chembiol.2016.06.011

A Continuous, Fluorogenic Sirtuin 2 Deacylase Assay: Substrate Screening and Inhibitor Evaluation

Autor: Andreas Stahl Madsen, Matthias Schiedel, Manfred Jung, Christian A. Olsen, Iacopo Galleano

Publikováno v: Journal of Medicinal Chemistry. 59:1021-1031

Sirtuins are important regulators of lysine acylation, which is implicated in cellular metabolism and transcriptional control. This makes the sirtuin class of enzymes interesting targets for development of small molecule probes with pharmaceutical po

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1daff00b5035f066649d454410c9900a
https://doi.org/10.1021/acs.jmedchem.5b01532