The design and synthesis of inhibitors of pantothenate synthetase.
Pantothenate synthetase catalyses the ATP-dependent condensation of D-pantoate and beta-alanine to form pantothenate. Ten analogues of the reaction intermediate pantoyl adenylate, in which the phosphodiester is replaced by either an ester or sulfamoyl group, were designed as potential inhibitors of the enzyme. The esters were all modest competitive inhibitors, the sulfamoyls were more potent, consistent with their closer structural similarity to the pantoyl adenylate intermediate.
Tuck
Kellie L
KL
University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW.
Saldanha
S Adrian
SA
Birch
Louise M
LM
Smith
Alison G
AG
Abell
Chris
C
D000255:Adenosine Triphosphate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D004952:Esters / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D010453:Peptide Synthases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017433:Protein Structure, Secondary; D013449:Sulfonamides / Q000737:chemistry; D013696:Temperature
D004791:Enzyme Inhibitors; D004952:Esters; D013449:Sulfonamides; D000255:Adenosine Triphosphate; D010453:Peptide Synthases; C022318:pantothenate synthetase