22248-65-3Relevant academic research and scientific papers
Lytic reactions of drugs with lipid membranes
Britt, Hannah M.,García-Herrero, Clara A.,Denny, Paul W.,Mosely, Jackie A.,Sanderson, John M.
, p. 674 - 680 (2019/01/24)
Propranolol is shown to undergo lipidation reactions in three types of lipid membrane: (1) synthetic single-component glycerophospholipid liposomes; (2) liposomes formed from complex lipid mixtures extracted from E. coli or liver cells; and (3) in cellulo in Hep G2 cells. Fourteen different lipidated propranolol homologues were identified in extracts from Hep G2 cells cultured in a medium supplemented with propranolol. This isolation of lipidated drug molecules from liver cells demonstrates a new drug reactivity in living systems. Acyl transfer from lipids to the alcoholic group of propranolol was favoured over transfer to the secondary amine. Migration of acyl groups from the alcohol to the amine was diminished. Other drugs that were examined did not form detectable levels of lipidation products, but many of these drugs did affect the lysolipid levels in model membranes. The propensity for a compound to induce lysolipid formation in a model system was found to be a predictor for phospholipidosis activity in cellulo.
Interfacial kinetic and binding properties of mammalian group IVB phospholipase A2 (cPLA2β) and comparison with the other cPLA2 isoforms
Ghomashchi, Farideh,Naika, Gajendra S.,Bollinger, James G.,Aloulou, Ahmed,Lehr, Matthias,Leslie, Christina C.,Gelb, Michael H.
experimental part, p. 36100 - 36111 (2011/12/16)
The cytosolic (group IV) phospholipase A2 (cPLA2s) family contains six members. We have prepared recombinant proteins for human α, mouse β, human γ, human δ, human ε, and mouse ζ cPLA2s and have studied their interfacial kinetic and binding properties in vitro. Mouse cPLA2β action on phosphatidylcholine vesicles is activated by anionic phosphoinositides and cardiolipin but displays a requirement for Ca2+ only in the presence of cardiolipin. This activation pattern is explained by the effects of anionic phospholipids and Ca2+ on the interfacial binding of mouse cPLA2β and its C2 domain to vesicles. Ca2+-dependent binding of mouse cPLA 2β to cardiolipin-containing vesicles requires a patch of basic residues near the Ca2+-binding surface loops of the C2 domain, but binding to phosphoinositide-containing vesicles does not depend on any specific cluster of basic residues. Human cPLA2δ also displays Ca 2+- and cardiolipin-enhanced interfacial binding and activity. The lysophospholipase, phospholipase A1, and phospholipase A2 activities of the full set of mammalian cPLA2s were quantified. The relative level of these activities is very different among the isoforms, and human cPLA2δ stands out as having relatively high phospholipase A1 activity. We also tested the susceptibility of all cPLA 2 family members to a panel of previously reported inhibitors of human cPLA2α and analogs of these compounds. This led to the discovery of a potent and selective inhibitor of mouse cPLA2β. These in vitro studies help determine the regulation and function of the cPLA2 family members.
Process for preparing lysophoshatidylcholine
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Page/Page column 7, (2010/11/08)
What is described is a process for preparing lysophosphatidylcholine by selective monoacylation of glycerophosphorylcholine (I), in the presence of an acylating agent and of dialkyltin derivatives, according to the following diagram: the process being particularly simple and having high overall yields.
