Inhibition of granulocyte-macrophage colony-stimulating factor (GM-CSF) activity by suramin and suramin analogues is correlated to interaction with the GM-CSF nucleotide-binding site.
Suramin and suramin analogues strongly inhibit both nucleotide interaction with the nucleotide-binding site of granulocyte-macrophage colony-stimulating factor (GM-CSF) and bioactivity of the molecule as assessed by competition photoaffinity labeling and cell proliferation assay, respectively. The half-maximal inhibition of cell proliferation by suramin occurs at 68 +/- 2.5 microM; three suramin analogues achieved comparable activity. The degree of competitive inhibition of nucleotide-binding by these compounds and the inhibition of GM-CSF bioactivity are correlated such that the compounds show similar rank-order by both of these methods. The strong interaction of suramin and related compounds with the nucleotide-binding site may mimic nucleotide-mediated inhibition of GM-CSF bioactivity and may be an important mechanism by which suramin acts as a pharmacological anti-growth factor agent.
Doukas
M
M
Veterans Affairs Medical Center, Lexington, Kentucky 40536-0093, USA.
Chavan
A
A
Gass
C
C
Nickel
P
P
Boone
T
T
Haley
B
B
D001665:Binding Sites; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D013498:Suramin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013498:Suramin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor