Poly-l-methionine Sulfoxide: A Biologically Inert Analogue of Dimethyl Sulfoxide with Solubilizing Potency

Abstract

Poly-l-methionine sulfoxide is a water-soluble polymer containing the sulfoxide moiety. The preparation and radiolabeling of this polymer is described and its bioeffects are compared with those of dimethyl sulfoxide. Poly-l-methionine sulfoxide is similar to dimethyl sulfoxide in that it is a potent solubilizer of lipophilic compounds in water. Although the partition coefficient of poly-l-methionine sulfoxide in 1-octanol-water is only 20 times lower than that of dimethyl sulfoxide, it was found not to penetrate into intracellular spaces. In contrast to dimethyl sulfoxide, poly-l-methionine sulfoxide and L-methionine sulfoxide were found to be ineffective in inducing differentiation in murineerythroleukemia cells and inhibiting differentiation of avian neural crest cells, suggesting that compounds effective in these processes must have the ability to penetrate into cells or membrane proteins. Overall lack of bioactivity of poly-l-methionine sulfoxide, combined with low toxicity (2g/kg, iv, in the mouse with no effect), makes this compound a suitable inert solubilizer and carrier for lipophilic drugs.