INHIBITION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) ACTIVITY BY SURAMIN AND SURAMIN ANALOGS IS CORRELATED TO INTERACTION WITH THE GM-CSF NUCLEOTIDE-BINDING SITE

Suramin and suramin analogues strongly inhibit both nucleotide interac tion with the nucleotide-binding site of granulocyte-macrophage colony -stimulating factor (GM-CSF) and bioactivity of the molecule as assess ed by competition photoaffinity labeling and cell proliferation assay, respectively, The half-maximal inhibition of cell proliferation by su ramin occurs at 68 +/- 2.5 mu M; three suramin analogues achieved comp arable activity, The degree of competitive inhibition of nucleotide-bi nding 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 inhibi tion of GM-CSF bioactivity and may be an important mechanism by which suramin acts as a pharmacological anti-growth factor agent.