Phospholipid analogs - chemoenzymatic syntheses and properties as enzyme effectors

Abstract

The synthesis of three types of phospholipid analogs by use of enzymes is described. The first group of compounds comprises 1,3-diacylglycerols modified at 2-position being regioisomers of natural glycero-phospholipids. According to Schneider et al. (J. Am. Oil Chem. Soc. 69 (1992), 955-960), glycerol was acylated with the vinyl esters of fatty acids by 1,3-selective lipase from Rhizomucor miehei. Modification of these regioisomerically pure 1,3-diacylglycerols in the 2-position by conventional chemical methods yielded 1,3-diacylglycero-2-phosphocholines or other amphiphilic compounds. such as 1,3-dilauroylglycero-2-phosphate or 1,3-dilauroylglycero-2-sulfate. The second group of newly synthesized compounds represent 1,2-dioleoyl-sn-glycero-3-phospholipids with N-heterocyclic head groups. They were obtained from 1,2-dioleoyl-sn-glycero-3-phosphocholine by transphosphatidylation with phospholipase D from cabbage or Streptomyces sp. in two-phase systems. These results prove that phospholipases D from both sources are able to transfer the phosphatidyl moiety even to secondary alcohols. Finally, it is demonstrated that phospholipase D is also appropriate to catalyze the transesterification of alkylphosphate esters, such as the conversion of octadecylphosphocholine into octadecylphosphoryl-N-(2-hydroxyethyl)-N-methylpiperidine. Selected compounds of the three classes of phospholipid analogs were used to study their effectory properties on phospholipase D. 1,3-Di-lauroylglycero-2-phosphocholine as well as alkylphosphate esters act as inhibitors of phospholipase D from cabbage, whereas the anionic amphiphiles 1,3-dilauroylglycero-2-phosphate and 1,3-dilauroylglycero-2-sulfate activate the enzyme similar to sodium dodecylsulfate.