Synthesis and inhibition properties of a series of pyranose derivatives towards a Zn-metalloproteinase from Saccharomonospora canescens

Pavlina Dolashka-Angelova, Raid J. Abdel-Jalil, Raed A. Al-Qawasmeh, Nicolina Stambolieva, Wolfgang Voelter

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2 Citations (Scopus)


The Zn-proteinase, isolated from Saccharomonospora canescens (NPS), shares many common features with thermolysin, but considerable differences are also evident, as far as the substrate recognition site is concerned. In substrates of general structure AcylAlaAlaPhe 4NA, this neutral proteinase cleaves only the arylamide bond (non-typical activity of Zn-proteinases), while thermolysin attacks the peptide bond Ala-Phe. Phosphoramidon is a powerful tight binding inhibitor for thermolysin and significantly less specific towards NPS. The Ki-values (65 μM for NPS vs 0.034 μM for thermolysin) differ nearly 2000-folds. This implies significant differences in the specificity of the corresponding subsites. The carbohydrate moiety is supposed to accommodate in the S1-subsite and the series of arabinopyranosides and glucopyranosides (12 compounds), which are assayed as inhibitors in a model system: NPS with SucAlaAlaPhe4NA as a substrate could be considered as mapping the S1-subsite of NPS. Members of the series with an additional ring (3,4-epithio, 3,4-anhydro-derivatives) turned out to be reasonably good competitive inhibitors (Ki ≈ 0.1-0.2 mM are of the same order as the Ki value for phosphoramidon). The structure of these compounds (8, 9, 11 and 12) seems to fit the size of the S1-subsite and due to an appropriately oriented OH-group in addition, to protect the active site Zn2+.

Original languageEnglish
Pages (from-to)2343-2347
Number of pages5
JournalCarbohydrate Research
Issue number16
Publication statusPublished - Nov 2 2010



  • Carbohydrate inhibitors
  • Neutral Zn-proteinase
  • S-Subsite

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Organic Chemistry

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