Pharmacological Concentrations of Suramin Inhibit the Binding of α2‐Macroglobulin to its Cell‐Surface Receptor

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Abstract
Suramin is a polysulfated drug used in the treatment of cancer and AIDS. High concentrations (1 mg/ ml) of suramin did not affect the ability of native α2‐macroglobulin (α2M) to inhibit proteinases nor did it prevent conversion of native α2M to the ‘fast’ receptor‐binding form. Nevertheless, pharmacological concentrations (below 250 μg/ml) of suramin prevented the interaction between methylamine‐activated α2M and its receptor, the low‐density‐lipoprotein‐receptor‐related protein. Inhibition was demonstrated at the molecular level and was not due to calcium sequestration by the drug, irreversible denaturation of the receptor, or a non‐specific polyanion effect (since heparin and dextran sulfate did not alter the binding of α2M). The ability of suramin to accelerate the dissociation of pre‐bound α2M was consistent with a non‐competitive mechanism of inhibition although the possibility of a competitive component cannot be eliminated. I discuss how the inhibition of α2M‐binding by suramin may contribute to the antiproliferative properties of this drug.