SYNTHESIS OF A NOVEL SIALIC-ACID DERIVATIVE (SIALYLPHOSPHOLIPID) AS AN ANTIROTAVIRAL AGENT

A novel sialylphospholipid (SPL) was synthesized from N-acetylneuramin ic acid (NeuAc) and phosphatidylcholine (PC) by a chemical and enzymat ic method and evaluated as an inhibitor of rotavirus. PC and 1,8-octan ediol were conjugated by transesterification reaction of Streptomyces phospholipase D (PLD) under a water-chloroform biphasic system to affo rd phosphatidyloctanol, which was condensed with a protected 2-chloro- 2-deoxyneuraminic acid derivative by using silver trifluoromethanesulf onate as an activator in chloroform and converted, after deprotection, to SPL. Rhesus monkey kidney cells (MA-104) were incubated with simia n (SA-11 strain) and human (MO strain) rotaviruses in the presence of SPL, and the cells infected were detected indirectly with anti-rotavir us antibody. SPL showed dose dependent inhibition against both virus s trains. The concentrations required for 50% inhibition (IC50) against SA-11 and MO were 4.35 and 16.1 mu M, respectively, corresponding to 1 0(3)- and 10(4)-fold increases in inhibition as compared to monomeric NeuAc.