Synthesis of bromoindolyl 4,7-di-O-methyl-Neu5Ac: specificity toward influenza A and B viruses.
N-Acetylneuraminic acid (Neu5Ac) was converted into the methyl ester methyl ketoside-8,9-epoxy derivative (8). Methylation of 8 followed by deprotection gave 4,7-di-O-methyl-Neu5Ac (10). Compound 10 was converted into the corresponding methyl ester-chloroacetate derivative, which was subsequently coupled to 5-bromo-indol-3-ol to give the chromogenic product (13). Deprotection of 13 gave 5-bromo-indol-3-yl 4,7-di-O-methyl-Neu5Ac (5). The product 5 was specifically cleaved by sialidase from either influenza A or influenza B virus to give an indigo-blue precipitate, but was not cleaved by several bacterial or viral sialidases tested. The properties of product 5 relative to a fluorescent substrate for sialidase were also documented.
Liav
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ZymeTx Inc., Oklahoma City, OK 73104, USA. liava@zymetx.com
Hansjergen
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Achyuthan
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Shimasaki
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D001173:Arthrobacter / Q000201:enzymology; D002236:Carbohydrate Conformation; D003016:Clostridium perfringens / Q000201:enzymology; D006801:Humans; D009980:Influenza A virus / Q000201:enzymology* / Q000302:isolation & purification; D009981:Influenza B virus / Q000201:enzymology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000175:diagnosis; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000201:enzymology; D013291:Streptococcus / Q000201:enzymology; D013379:Substrate Specificity
C121208:5-bromoindolyl-4,7-di-O-methyl-N-acetylneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid