PHARMACOLOGICAL CONCENTRATIONS OF SURAMIN INHIBIT THE BINDING OF ALPHA(2)-MACROGLOBULIN TO ITS CELL-SURFACE RECEPTOR

Suramin is a polysulfated drug used in the treatment of cancer and AID S. High concentrations (1 mg/ml) of suramin did not affect the ability of native alpha(2)-macroglobulin (alpha(2)M) to inhibit proteinases n or did it prevent conversion of native alpha(2)M to the 'fast' recepto r-binding form, Nevertheless, pharmacological concentrations (below 25 0 mu g/ml) of suramin prevented the interaction between methylamine-ac tivated alpha(2)M and its receptor, the low-density-lipoprotein-recept or-related protein, Inhibition was demonstrated at the molecular level and was not due to calcium sequestration by the drug, irreversible de naturation of the receptor, or a non-specific polyanion effect (since heparin and dextran sulfate did not alter the binding of alpha(2)M). T he ability of suramin to accelerate the dissociation of pre-bound alph a(2)M was consistent with a noncompetitive mechanism of inhibition alt hough the possibility of a competitive component cannot be eliminated. I discuss how the inhibition of alpha(2)M-binding by suramin may cont ribute to the antiproliferative properties of this drug.