Identifying protein kinase inhibitors using an assay based on inhibition of aerial hyphae formation in Streptomyces.
We have identified a strain of Streptomyces in which aerial hyphae formation appears to be especially sensitive to inhibition by protein kinase inhibitors. Using this assay, a number of bacterial cultures have been screened and novel inhibitors of eukaryotic protein kinases have been identified. Since M. tuberculosis possesses multiple eukaryotic-like protein kinase genes, we tested the active kinase inhibitors for the inhibition of mycobacterial growth and obtained several potent compounds. This identifies a new biochemical class of antimycobacterial agents.
Waters
Barbara
B
Cubist Pharmaceuticals, Inc., Vancouver, BC, Canada.
Saxena
Geeta
G
Wanggui
Yangsheng
Y
Kau
David
D
Wrigley
Stephen
S
Stokes
Richard
R
Davies
Julian
J
D001407:Bacillus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011549:Pseudomonas / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013171:Spores, Bacterial / Q000187:drug effects / Q000254:growth & development; D013302:Streptomyces / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D055666:Lipopeptides; D008074:Lipoproteins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; C459019:cyclomarin A; C062796:viscosin; C066137:depsidomycin; C009365:surfactin peptide; C458999:pyridomycin