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Bisphosphonic acids and related compounds as inhibitors of nucleotide- and polyphosphate-processing enzymes: A PPK1 and PPK2 case study.

Małgorzata Burda-GrabowskaKatarzyna MacegoniukRobert FlickBoguslaw P NocekAndrzej JoachimiakAlexander F YakuninArtur MuchaŁukasz Berlicki
Published in: Chemical biology & drug design (2018)
Bisphosphonic acids, which are structural analogs of pyrophosphate, constitute a class of compounds with very high potential for the construction of effective inhibitors of enzymes operating on oligo- and polyphosphates. The bisphosphonate-based methodology was applied for the discovery of inhibitors of two families of polyphosphate kinases (PPK1 and PPK2). Screening of thirty-two structurally diverse bisphosphonic acids and related compounds revealed several micromolar inhibitors of both enzymes. Importantly, selectivity of bisphosphonates could be achieved by application of the appropriate side chain.
Keyphrases
  • small molecule
  • molecular docking
  • human health