title: Synthesis of charged amphipathic nitroxide lipid spin labels and an example of their application in membrane studies.
abstract: The synthesis of a series of amphipathic nitroxide lipid spin labels is reported. Thus, 12-proxylhexadecanol has been converted into the versatile fatty acid spin label 14-proxylstearic acid. This substance was used to prepare 14-proxylstearyltrimethylammonium methanesulfonate, a positively charged label, and 14-proxylstearylmethyl phosphate sodium salt, a negatively charged label. Also prepared in the doxyl series were quaternary ammonium salts derived from 16-doxyl- and 7-doxylstearic acid. The positively charged and negatively charged proxyl labels were used in a preliminary experiment to investigate the role of charge in their interaction with reconstituted cytochrome oxidase. The average binding affinity of the negatively charged label is approximately 2-fold higher than that of the positively charged label at pH 7.4. At pH 5.5 the average relative affinity for negatively charged label is about 3.5-fold higher than that of positively charged label, suggesting that the ionizable group(s) on the protein can interact with the lipid headgroup.
mesh_terms: D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D003576:Electron Transport Complex IV / Q000378:metabolism; D007202:Indicators and Reagents; D008563:Membrane Lipids / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D008566:Membranes / Q000648:ultrastructure*; D008722:Methods; D013113:Spin Labels / Q000138:chemical synthesis*
chemical_list: D003497:Cyclic N-Oxides; D007202:Indicators and Reagents; D008563:Membrane Lipids; D008565:Membrane Proteins; D013113:Spin Labels; D003576:Electron Transport Complex IV