%0 Journal Article
%T Bisphosphonic acids and related compounds as inhibitors of nucleotide- and polyphosphate-processing enzymes: A PPK1 and PPK2 case study.
%A Burda-Grabowska M
%A Macegoniuk K
%A Flick R
%A Nocek BP
%A Joachimiak A
%A Yakunin AF
%A Mucha A
%A Berlicki Ł
%J Chem Biol Drug Des
%V 93
%N 6
%D 06 2019
%M 30484959
%F 2.873
%R 10.1111/cbdd.13439
%X 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.