EPR spectroscopic analysis of binding sites of a cancerostatic agent on erythrocyte membranes.
A biologically highly active antitumor agent, chloroethyl-nitrosourea-piperidine-N-oxyl, was found to bind covalently to sulfhydryl groups of membrane proteins of erythrocytes. The agent penetrates the erythrocyte membrane very easily within three minutes. Mainly two different binding sites are distinguishable with rather high rotational mobility of the NO-moiety and high polarity of their environment. The lowered broadening of bound label suggests pocket-like binding sites with a limited accessibility for paramagnetic ions. Besides common concepts that antitumor agents often bind to DNA and inhibit cell proliferation, further targets on plasma membranes are taken into consideration for antitumor agents.
D000477:Alkylating Agents / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003497:Cyclic N-Oxides / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005038:Ethylnitrosourea / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008560:Membrane Fluidity; D013113:Spin Labels; D013696:Temperature
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D013113:Spin Labels; C045032:1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)-1-nitrosourea; D005038:Ethylnitrosourea