Synthesis of a novel sialic acid derivative (sialylphospholipid) as an antirotaviral agent.
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.
Koketsu
M
M
Central Research Laboratories, Taiyo Kagaku Company, Ltd., Mie, Japan. koketsu@apchem.gifu-u.ac.jp
Nitoda
T
T
Sugino
H
H
Juneja
L R
LR
Kim
M
M
Yamamoto
T
T
Abe
N
N
Kajimoto
T
T
Wong
C H
CH
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
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