TY - JOUR

T1 - Bisphosphonic acids and related compounds as inhibitors of nucleotide- and polyphosphate-processing enzymes

T2 - A PPK1 and PPK2 case study

AU - Burda-Grabowska, Małgorzata

AU - Macegoniuk, Katarzyna

AU - Flick, Robert

AU - Nocek, Boguslaw P

AU - Joachimiak, Andrzej

AU - Yakunin, Alexander F

AU - Mucha, Artur

AU - Berlicki, Łukasz

N1 - © 2018 John Wiley & Sons A/S.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - Diphosphonates/pharmacology

KW - Enzyme Inhibitors/pharmacology

KW - Isoenzymes/antagonists & inhibitors

KW - Nucleotides/metabolism

KW - Phosphotransferases (Phosphate Group Acceptor)/antagonists & inhibitors

KW - Polyphosphates/metabolism

U2 - 10.1111/cbdd.13439

DO - 10.1111/cbdd.13439

M3 - Article

C2 - 30484959

VL - 93

SP - 1197

EP - 1206

JO - Chemical biology & drug design

JF - Chemical biology & drug design

SN - 1747-0277

IS - 6

ER -