A potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species.
A potent inhibitor of seryl tRNA synthetase, designated SB-217452 has been isolated from Streptomyces sp. ATCC 700974. The fermentation, isolation, structure elucidation and some properties are described. SB-217452 showed inhibitory activity against both Staphylococcus aureus and rat seryl tRNA synthetases, with similar IC50 values of approximately 8 nM. The inhibitor is the serine linked nucleoside moiety of the antibiotic albomycin delta2. In contrast to albomycin delta2, SB-217452 showed only very weak antibacterial activity against a limited range of microorganisms. The compound has not been previously reported as a naturally occurring metabolite. In addition to SB-217452, albomycin delta2 Fe3+ complex and the novel Al3+ complex were isolated from the fermentation. These complexes had no seryl tRNA synthetase inhibitory activity.
Stefanska
A L
AL
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Fulston
M
M
Houge-Frydrych
C S
CS
Jones
J J
JJ
Warr
S R
SR
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011744:Pyrimidinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D012714:Serine-tRNA Ligase / Q000037:antagonists & inhibitors*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013211:Staphylococcus aureus / Q000201:enzymology; D013302:Streptomyces / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D013876:Thiophenes; C421167:SB 217452; D012714:Serine-tRNA Ligase