SYNTHESIS OF PSEUDO-PHOSPHOLIPIDS BY PHOS PHOLIPASE D-CATALYZED TRANSPHOSPHATIDYLATION

We found that phospholipase D from Streptomyces sp.(PLDP) effectively catalyzed transphosphatidylation, i.e., the regiospecific transfer of the phosphatidyl residue from phosphatidylcholines to alkanols. The sc ope of this enzymatic reaction was investigated in detail to develop a n efficient method for preparing various phospholipid derivatives. Usi ng this enzymatic method, 5'-O-phosphatidyl derivatives of antitumor n ucleosides were successfully synthesized to identify potent antitumor drugs. 5'-O-Phosphatidyl derivatives of DMDC (2'-deoxy-2'-methylenecyt idine) and CNDAC [1-(2-C o-2-deoxy-beta-D-arabino-pentofuranosyl)cytos ine], antitumor nucleosides developed by us, showed significant antitu mor effects in mice which clearly surpassed those of parent compounds. We have also demonstrated that 5'-O-phosphatidylnucleosides can be us ed as a drug delivery system for lymph: 5'-O-phosphatidyl-5-fluorourid ine given orally is absorbed via the deacylation-reacylation cycle, a specific pathway for natural phospholipids, to be transported selectiv ely to the lymph.