A F-19 NMR-STUDY OF INTERACTIONS BETWEEN THE ATP-CITRATE LYASE INHIBITOR SB-200517 AND MODEL MEMBRANES

Fluorine-19 NMR (F-19-NMR) has been used to study the properties of SE -200517 (I), an inhibitor of the hepatic enzyme ATP-citrate lyase (ACL ), in small sonicated unilamellar dimyristoyl phosphatidylcholine (DMP C) vesicles, SUVs. Two relatively sharp signals are observed in this e nvironment, only the lower field of which is broadened by the paramagn etic relaxation-enhancing probe Mn2+. This suggests that the splitting observed in SUVs is due to the slightly different environments experi enced by fluorine atoms of inhibitor molecules localised to either the inner (higher field signal) or the outer (lower field signal) leaflet of the vesicles, The presence of fluorine in the compound thus provid es a quick and convenient method of studying its partitioning into non -aqueous environments; such partitioning can have significant implicat ions for bio-availabilty.