University of Oulu

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,

Adenosine analogs bearing phosphate isosteres as human MDO1 ligands

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Author: Zhang, Yuezhou1; Jumppanen, Mikael1; Maksimainen, Mirko M.2;
Organizations: 1Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014 University of Helsinki, Finland
2Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, FI-90014 University of Oulu, Finland
3Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, FI-00014 University of Helsinki, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
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Language: English
Published: Elsevier, 2018
Publish Date: 2020-02-13


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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Series: Bioorganic & medicinal chemistry
ISSN: 0968-0896
ISSN-E: 1464-3391
ISSN-L: 0968-0896
Volume: 26
Issue: 8
Pages: 1588 - 1597
DOI: 10.1016/j.bmc.2018.02.006
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This study was supported by grants from the Academy of Finland (Project 257685 for GBG, 287063 and 294085 for LL), China Scholarship Council (Grant no. 2009629110), University of Helsinki, Biocenter Oulu and Sigrid Juséliuksen Säätiö. Y.Z. and H.V. thank the Doctoral Program in Informational and Structural Biology for organizing graduate studies.
Academy of Finland Grant Number: 287063
Detailed Information: 287063 (Academy of Finland Funding decision)
294085 (Academy of Finland Funding decision)
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license