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Characterization of cyclocreatine‐membrane interactions by electron paramagnetic resonance spectroscopy
Author(s) -
Smith Virginia F.,
Stampfler Jeremiah B.,
Dillner Debra K.,
Elgebaly Salwa A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb122
Subject(s) - electron paramagnetic resonance , site directed spin labeling , chemistry , lipid bilayer , phospholipid , nitroxide mediated radical polymerization , spin label , liposome , biophysics , bilayer , membrane , biochemistry , nuclear magnetic resonance , organic chemistry , polymerization , biology , physics , radical polymerization , polymer
Cyclocreatine, a synthetic analog of the naturally‐occurring energy molecule creatine, is known to have medically‐important roles in cardioprotection and the prevention of neurodegeneration when administered alone or in conjunction with other agents. In each case, it is necessary for the cyclocreatine (CCr) molecule to cross a lipid bilayer to reach cell compartments where endogenous enzymes convert CCr to its active form, phosphocyclocreatine (PCCr). We have developed an in vitro system to study the interactions of CCr and PCCr with phospholipid headgroups and acyl chains using electron paramagnetic resonance (EPR) spectroscopy to monitor changes in the mobility of nitroxide‐labelled phospholipids in liposmes formed from bovine heart and brain lipid extracts. Cyclocreatine can be easily synthesized, using literature procedures, from chloroacetic acid and ethylene diamine. Phosphorylation of CCr with POCl3 yields PCCr. Moving the spin label to various positions along the acyl chain and headgroup made it possible to compare the effects of the two compounds at various depths of the membrane bilayer and to obtain important information about lipid mobility and dynamics. Preliminary results suggest that the presence of CCR reduces mobility of the lipid head group in a concentration‐dependent manner and that heart and brain liposomes have different responses to CCr and PCCr.