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.
Original language | English (US) |
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Pages (from-to) | 1588-1597 |
Number of pages | 10 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 26 |
Issue number | 8 |
DOIs | |
State | Published - May 1 2018 |
Externally published | Yes |
Keywords
- Adenosine analogs
- Adenosine diphosphate ribose
- Human macrodomain-containing protein 1
- MDO1
- Macrodomain
- Mono-ADP-ribosylhydrolase
- Phosphate isosteres
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry