Phosphatidic acid is a specific activator of phosphatidylinositol-4-phosphate kinase.

To overcome the many hurdles preventing the use of antiviral and anticancer nucleosides as therapeutics, the development of a prodrug methodology (i.e., pronucleotide) for the in vivo delivery of nucleotides has been proposed as a solution. The ideal pronucleotide should be non-toxic, stable in plasma and blood, capable of being i. v. and/or orally dosed, and intracellularly convertible to the corresponding nucleotide. Although this goal has yet to be achieved, many clever and imaginative pronucleotide approaches have been developed, which are likely to be important pharmacological tools. This review will discuss the major advances and future directions of the emerging field of antiviral and anticancer pronucleotide design and development.

Pronucleotides: toward the in vivo delivery of antiviral and anticancer nucleotides.

Phospholipase D in cell signalling and its relationship to phospholipase C

Minireview : nucleotide prodrugs

Lipophilic prodrugs designed for intestinal lymphatic transport

A facile one-step synthesis of 5'-phosphatidylnucleosides by an enzymatic two-phase reaction

Phospholipase D from Streptomyces effectively catalyzed the transfer reaction of the phosphatidyl residue from 3-sn-phosphatidylcholine to the 5'-hydroxyl group of nuclesides in a two-phase system. Thus, a variety of 5'-(3-sn-phosphatidyl)nucleosides could be readily prepared in high yields by means of this reaction. Among them, phosphatidyl-FUR (3b), phosphatidyl-Ara FC (8b), and phoshatidyl-neplanocin A (12b) each produced a significant increase in the life span mice bearing i.p.-implanted P388 leukemia, being more effective than the parent nucleosides.

A facile enzymatic synthesis of 5'-(3-sn-phosphatidyl)nucleosides and their antileukemic activities.

Nucleosides and nucleotides—CXXXVII. Antitumor phospholipids with 5-fluorouridine as a cytotoxic polar-head: Synthesis of 5′-phosphatidyl-5-fluorouridines by phospholipase d-catalyzed transphosphatidylation

PURPOSE:To produce a phospholipid derivative in good yield, by reacting a glycerophospholipid with a specific heterocyclic compound in the presence of phospholipase D-P. CONSTITUTION:A glycerophospholipid expressed by formula I [R1-2 are acyl or aliphatic hydrocarbon group; R3 is formula II; R4-5 are all H or each differently H, carboxyl(methyl)amino, dimethylamino, trimethylamino, hydroxyl, hydroxymethyl or inositol] is reacted with a heterocyclic compound expressed by the formula III (NS is organic residue linked with primary hydroxyl group) in the presence of 0.01-100 units phospholipase D-P per 1g glycerophospholipid in a bilayer system solvent consisting of an organic solvent (e.g. benzene) and buffer having 3-9pH at 20-60 deg.C for 30min-30hr to provide the aimed phospholipid derivative expressed by formula IV or salt thereof.

Shigeyuki Imamura

Papers

A facile one-step synthesis of 5'-phosphatidylnucleosides by an enzymatic two-phase reaction

A facile enzymatic synthesis of 5'-(3-sn-phosphatidyl)nucleosides and their antileukemic activities.

Nucleosides and nucleotides—CXXXVII. Antitumor phospholipids with 5-fluorouridine as a cytotoxic polar-head: Synthesis of 5′-phosphatidyl-5-fluorouridines by phospholipase d-catalyzed transphosphatidylation

Production of phospholipid derivative