The biologic activity of polyanions: Past history and new prospectives

The toxicology of synthetic polyanions relates to molecular weight. This developed from experience with pyran copolymer (divinyl ether maleic anhydride copolymer), which was tested clinically as an antitumor agent and found to be too toxic for continued clinical trial. Synthetic polyanions of low molecular weight are potent stimuli to macrophage phagocytic function and possess antitumor activity. Increased host resistance to pathogens including bacteria, fungi, viruses, and trypanosomes is seen. In contrast to lower‐molecular‐weight fractions, higher‐molecular‐weight samples inhibit macrophage function, and apparently increased molecular weight > 15,000 is necessary for antiviral and immunologic stimulating capacity. One possible mechanism for the action of polyanions may relate to redistribution of calcium ions within the cell and increasing cyclic GMP activity. This is a redefinition for the role of polyanions in sol–gel alteration in cytoplasm. The killing effect of the polyanion‐activated macrophage on tumor cells resembles that of the polyanion on the nucleus. Polyanions may be potent controllers of the stability of DNA within the nucleus and can act to derepress cells to turn on protein synthesis or, alternatively, inhibit enzymes involved in virus synthesis and control of RNA or DNA polymerase. Thus, they are cogent tools in an understanding of the physiology of nuclear interaction. Biological use for these agents can be developed not only in clinical approaches to inhibition of tumor or viral infection, but to eliminate plutonium, and provide selective enzyme inhibition and protein interaction which allows for isolation, neutralization, and characterization of blood and tissue protein and glycoprotein fractions vital for a wide range of pathophysiology.