title: Tuning Cerium(IV)-Assisted Hydrolysis of Phosphatidylcholine Liposomes under Mildly Acidic and Neutral Conditions.
abstract: With the goal of designing a lysosomal phospholipase mimic, we optimized experimental variables to enhance Ce(IV) -assisted hydrolysis of phosphatidylcholine (PC) liposomes. Our best result was obtained with the chelating agent bis-tris propane (BTP). Similar to the hydrolytic enzyme, Ce(IV) -assisted hydrolysis of PC phosphate ester bonds was higher at lysosomal pH (∼4.8) compared to pH 7.2. In the presence of BTP, the average cleavage yield at ∼pH 4.8 and 37 °C was: 67±1 %, 5.7-fold higher than at ∼pH 7.2 and roughly equivalent to the percent of phospholipid found on the metal-accessible exo leaflet of small liposomes. No Ce(IV) precipitation was observed. When BTP was absent, there was significant turbidity, and the amount of cleavage at ∼pH 4.8 (69±1 %) was 2.1-fold higher than the yield obtained at ∼pH 7.2. Our results show that BTP generates homogenous solutions of Ce(IV) that hydrolyze phosphatidylcholine with enhanced selectivity for lysosomal pH.
authors.affiliation: Department of Chemistry, Georgia State University, P.O. Box 3965, Atlanta, GA 30302-3965 (USA).
authors.forename: Dominique E
authors.initials: DE
authors.lastname: Williams
authors.affiliation: Department of Chemistry, Georgia State University, P.O. Box 3965, Atlanta, GA 30302-3965 (USA).
authors.forename: Kanchan
authors.initials: K
authors.lastname: Basnet
authors.affiliation: Department of Chemistry, Georgia State University, P.O. Box 3965, Atlanta, GA 30302-3965 (USA). kbgrant@gsu.edu.
authors.forename: Kathryn B
authors.initials: KB
authors.lastname: Grant
mesh_terms: D002563:Cerium / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008081:Liposomes / Q000737:chemistry*; D008247:Lysosomes / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry*; D014325:Tromethamine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; D014325:Tromethamine; D002563:Cerium; C034249:1,3-bis(tris(hydroxymethyl)methylamino)propane
keywords: hydrolysis; lanthanides; liposomes; lysosomes; phosphate ester