title: Synthesis of a novel sialic acid derivative (sialylphospholipid) as an antirotaviral agent.
abstract: A novel sialylphospholipid (SPL) was synthesized from N-acetylneuraminic acid (NeuAc) and phosphatidylcholine (PC) by a chemical and enzymatic method and evaluated as an inhibitor of rotavirus. PC and 1,8-octanediol were conjugated by transesterification reaction of Streptomyces phospholipase D (PLD) under a water-chloroform biphasic system to afford phosphatidyloctanol, which was condensed with a protected 2-chloro-2-deoxyneuraminic acid derivative by using silver trifluoromethanesulfonate as an activator in chloroform and converted, after deprotection, to SPL. Rhesus monkey kidney cells (MA-104) were incubated with simian (SA-11 strain) and human (MO strain) rotaviruses in the presence of SPL, and the cells infected were detected indirectly with anti-rotavirus antibody. SPL showed dose dependent inhibition against both virus strains. The concentrations required for 50% inhibition (IC50) against SA-11 and MO were 4.35 and 16.1 microM, respectively, corresponding to 10(3)- and 10(4)-fold increases in inhibition as compared to monomeric NeuAc.
authors.affiliation: Central Research Laboratories, Taiyo Kagaku Company, Ltd., Mie, Japan. koketsu@apchem.gifu-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Koketsu
authors.forename: T
authors.initials: T
authors.lastname: Nitoda
authors.forename: H
authors.initials: H
authors.lastname: Sugino
authors.forename: L R
authors.initials: LR
authors.lastname: Juneja
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Abe
authors.forename: T
authors.initials: T
authors.lastname: Kajimoto
authors.forename: C H
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010712:Phosphatidic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012401:Rotavirus / Q000187:drug effects*; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013302:Streptomyces / Q000201:enzymology
chemical_list: D000998:Antiviral Agents; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D012794:Sialic Acids; C108923:alpha-(N-acetylneuraminyl)phosphatidyloctanediol; D010739:Phospholipase D; D019158:N-Acetylneuraminic Acid