PHOSPHOLIPID ANALOGS - CHEMOENZYMATIC SYNTHESES AND PROPERTIES AS ENZYME EFFECTORS

The synthesis of three types of phospholipid analogs by use of enzymes is described. The first group of compounds comprises 1,3-diacylglycer ols modified at 2-position being regioisomers of natural glycerophosph olipids. According to Schneider et al. (J. Am. Oil Chem. Sec. 69 (1992 ), 955-960), glycerol was acylated with the vinyl esters of fatty acid s by 1,3-selective lipase from Rhizomucor miehei. Modification of thes e regioisomerically pure 1,3-diacylglycerols in the 2-position by conv entional chemical methods yielded 1,3-diacylglycero-2-phosphocholines or other amphiphilic compounds, such as 1,3-dilauroylglycero-2-phospha te or 1,3-dilauroylglycero-2-sulfate. The second group of newly synthe sized compounds represent 1,2-dioleoyl-sn-glycero-3 phospholipids with N-heterocyclic head groups. They were obtained from 1,2-dioleoyl-sn-g lycero-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 demons trated that phospholipase D is also appropriate to catalyze the transe sterification of alkylphosphate esters, such as the conversion of octa decylphosphocholine into lphosphoryl-N-(2-hydroxyethyl)-N-methylpiperi dine. Selected compounds of the three classes of phospholipid analogs were used to study their effectory properties on phospholipase D. 1,3- Dilauroylglycero-2-phosphocholine as well as alkylphosphate esters act as inhibitors of phospholipase D from cabbage, whereas the anionic am phiphiles 1,3-dilauroylglycero-2-phosphate and 1,3-dilauroylglycero-2- sulfate activate the enzyme similar to sodium dodecylsulfate.