Adenosine analogs bearing phosphate isosteres as human MDO1 ligands
Zhang, Yuezhou; Jumppanen, Mikael; Maksimainen, Mirko M.; Auno, Samuli; Awol, Zulfa; Ghemtio, Léo; Venkannagari, Harikanth; Lehtiö, Lari; Yli-Kauhaluoma, Jari; Xhaard, Henri; Boije af Gennäs, Gustav (2018-02-13)
Yuezhou Zhang, Mikael Jumppanen, Mirko M. Maksimainen, Samuli Auno, Zulfa Awol, Léo Ghemtio, Harikanth Venkannagari, Lari Lehtiö, Jari Yli-Kauhaluoma, Henri Xhaard, Gustav Boije af Gennäs, Adenosine analogs bearing phosphate isosteres as human MDO1 ligands, Bioorganic & Medicinal Chemistry, Volume 26, Issue 8, 2018, Pages 1588-1597, ISSN 0968-0896, https://doi.org/10.1016/j.bmc.2018.02.006
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
https://creativecommons.org/licenses/by-nc-nd/4.0/
https://urn.fi/URN:NBN:fi-fe201902266264
Tiivistelmä
Abstract
The human O-acetyl-ADP-ribose deacetylase MDO1 is a mono-ADP-ribosylhydrolase involved in the reversal of post-translational modifications. Until now MDO1 has been poorly characterized, partly since no ligand is known besides adenosine nucleotides. Here, we synthesized thirteen compounds retaining the adenosine moiety and bearing bioisosteric replacements of the phosphate at the ribose 5′-oxygen. These compounds are composed of either a squaryldiamide or an amide group as the bioisosteric replacement and/or as a linker. To these groups a variety of substituents were attached such as phenyl, benzyl, pyridyl, carboxyl, hydroxy and tetrazolyl. Biochemical evaluation showed that two compounds, one from both series, inhibited ADP-ribosyl hydrolysis mediated by MDO1 in high concentrations.
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