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) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe201902266264 |
Language: | English |
Published: |
Elsevier,
2018
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Publish Date: | 2020-02-13 |
Description: |
AbstractThe 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. see all
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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 |
OADOI: | https://oadoi.org/10.1016/j.bmc.2018.02.006 |
Type of Publication: |
A1 Journal article – refereed |
Field of Science: |
1182 Biochemistry, cell and molecular biology |
Subjects: | |
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 294085 |
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 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |