Adenosine analogs bearing phosphate isosteres as human MDO1 ligands

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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 languageEnglish (US)
Pages (from-to)1588-1597
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number8
StatePublished - May 1 2018
Externally publishedYes


  • 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


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