Nucleoside triphosphate mimicry: a sugar triazolyl nucleoside as an ATP-competitive inhibitor of B. anthracis pantothenate kinase.
The synthesis of a library of nucleoside triphosphate mimetics is described where the Mg(2+) chelated triphosphate sidechain is replaced by an uncharged methylene-triazole linked monosaccharide sidechain. The compounds have been evaluated as inhibitors of Bacillus anthracis pantothenate kinase and a competitive inhibitor has been identified with a K(i) that is 3-fold lower than the K(m) value of ATP.
Rowan
Andrew S
AS
School of Chemistry and Chemical Engineering, David Keir Building, Stranmillis Road, Queen's University Belfast, Belfast, BT9 5AG.
Nicely
Nathan I
NI
Cochrane
Nicola
N
Wlassoff
Wjatschesslaw A
WA
Claiborne
Al
A
Hamilton
Chris J
CJ
D000255:Adenosine Triphosphate / Q000378:metabolism*; D001408:Bacillus anthracis / Q000201:enzymology*; D001667:Binding, Competitive; D032701:Biomimetics; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D009705:Nucleosides / Q000737:chemistry*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011122:Polyphosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry*
D004791:Enzyme Inhibitors; D009705:Nucleosides; D011122:Polyphosphates; D014230:Triazoles; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; C005692:triphosphoric acid