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

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

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.
Alkuperäiskielienglanti
LehtiBioorganic & Medicinal Chemistry
Vuosikerta26
Numero8
Sivut1588-1597
Sivumäärä10
ISSN0968-0896
DOI - pysyväislinkit
TilaJulkaistu - 1 toukokuuta 2018
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 317 Farmasia

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