Adenosine analogs bearing phosphate isosteres as human MDO1 ligands

Yuezhou Zhang, Antti Mikael Jumppanen, Mirko M. Maksimainen, Atte Samuli Auno, Zulfa Awol , Leo Ghemtio, Harikanth Venkannagari, Lari Lehtiö, Jari Yli-Kauhaluoma, Henri Xhaard, Gustav Boije af Gennäs

Research output: Contribution to journalArticleScientificpeer-review

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 50-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. (C) 2018 Elsevier Ltd. All rights reserved.
Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Volume26
Issue number8
Pages (from-to)1588-1597
Number of pages10
ISSN0968-0896
DOIs
Publication statusPublished - 1 May 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy
  • Adenosine analogs
  • Adenosine diphosphate ribose
  • Mono-ADP-ribosylhydrolase
  • Human macrodomain-containing protein 1
  • MDO1
  • Macrodomain
  • Phosphate isosteres
  • MACRO DOMAIN
  • BINDING
  • LRP16
  • CARCINOMA
  • PROTEINS
  • RECEPTOR
  • FAMILY
  • CELLS
  • MODEL

Cite this

Zhang, Yuezhou ; Jumppanen, Antti Mikael ; Maksimainen, Mirko M. ; Auno, Atte Samuli ; Awol , Zulfa ; Ghemtio, Leo ; Venkannagari, Harikanth ; Lehtiö, Lari ; Yli-Kauhaluoma, Jari ; Xhaard, Henri ; Boije af Gennäs, Gustav. / Adenosine analogs bearing phosphate isosteres as human MDO1 ligands. In: Bioorganic & Medicinal Chemistry. 2018 ; Vol. 26, No. 8. pp. 1588-1597.
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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 50-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. (C) 2018 Elsevier Ltd. All rights reserved.",
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author = "Yuezhou Zhang and Jumppanen, {Antti Mikael} and Maksimainen, {Mirko M.} and Auno, {Atte Samuli} and Zulfa Awol and Leo Ghemtio and Harikanth Venkannagari and Lari Lehti{\"o} and Jari Yli-Kauhaluoma and Henri Xhaard and {Boije af Genn{\"a}s}, Gustav",
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Adenosine analogs bearing phosphate isosteres as human MDO1 ligands. / Zhang, Yuezhou; Jumppanen, Antti Mikael; Maksimainen, Mirko M.; Auno, Atte Samuli; Awol , Zulfa; Ghemtio, Leo; Venkannagari, Harikanth; Lehtiö, Lari; Yli-Kauhaluoma, Jari; Xhaard, Henri; Boije af Gennäs, Gustav.

In: Bioorganic & Medicinal Chemistry, Vol. 26, No. 8, 01.05.2018, p. 1588-1597.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Zhang, Yuezhou

AU - Jumppanen, Antti Mikael

AU - Maksimainen, Mirko M.

AU - Auno, Atte Samuli

AU - Awol , Zulfa

AU - Ghemtio, Leo

AU - Venkannagari, Harikanth

AU - Lehtiö, Lari

AU - Yli-Kauhaluoma, Jari

AU - Xhaard, Henri

AU - Boije af Gennäs, Gustav

PY - 2018/5/1

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N2 - 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 50-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. (C) 2018 Elsevier Ltd. All rights reserved.

AB - 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 50-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. (C) 2018 Elsevier Ltd. All rights reserved.

KW - 317 Pharmacy

KW - Adenosine analogs

KW - Adenosine diphosphate ribose

KW - Mono-ADP-ribosylhydrolase

KW - Human macrodomain-containing protein 1

KW - MDO1

KW - Macrodomain

KW - Phosphate isosteres

KW - MACRO DOMAIN

KW - BINDING

KW - LRP16

KW - CARCINOMA

KW - PROTEINS

KW - RECEPTOR

KW - FAMILY

KW - CELLS

KW - MODEL

U2 - 10.1016/j.bmc.2018.02.006

DO - 10.1016/j.bmc.2018.02.006

M3 - Article

VL - 26

SP - 1588

EP - 1597

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

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ER -