title: Synthesis of enantiopure 2-carba-cyclic phosphatidic acid and effects of its chirality on biological functions.
abstract: Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator, which has a quite unique cyclic phosphate ring at sn-2 and sn-3 positions of the glycerol backbone. We have designed and chemically synthesized several metabolically stabilized derivatives of cPA. 2-Carba-cPA (2ccPA) is one of the synthesized compounds in which the phosphate oxygen was replaced with a methylene group at the sn-2 position, and it showed much more potent biological activities than natural cPA. Here, we developed a new method of 2ccPA enantiomeric synthesis. And we examined the effects of 2ccPA enantiomers on autotaxin (ATX) activity, cancer cell invasion and nociceptive reflex. As well as racemic-2ccPA, both enantiomers showed inhibitory effects on ATX activity, cancer cell invasion and nociceptive reflex. As their effects were not significantly different from each other, the chirality of 2ccPA may not be critical for these biological functions of 2ccPA.
authors.affiliation: Graduate School of Humanities and Sciences, Department of Life Science, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Nozaki
authors.forename: Mari
authors.initials: M
authors.lastname: Gotoh
authors.forename: Harumi
authors.initials: H
authors.lastname: Hotta
authors.forename: Shuwa
authors.initials: S
authors.lastname: Hanazawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Kimiko
authors.initials: K
authors.lastname: Murakami-Murofushi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D002465:Cell Movement / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013127:Spinal Nerves / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured; D000099189:Lysophospholipase D
chemical_list: D017077:Culture Media, Conditioned; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D010712:Phosphatidic Acids; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C558317:2-carba-cyclic phosphatidic acid