The synthesis and enzymatic incorporation of sialic acid derivatives for use as tools to study the structure, activity, and inhibition of glycoproteins and other glycoconjugates.
Methods have been developed for the enzymatic synthesis of complex carbohydrates and glycoproteins containing in the sialic acid moiety the heavy metal mercury or the transition-state analog phosphonate of the influenza C 9-O-acetyl-neuraminic acid esterase-catalyzed reaction. 5-Acetamido-3, 5-dideoxy-9-methylphosphono-beta-D-glycero-D-galacto-nonulopyra nosidonic acid (1), 5-acetamido-3,5-dideoxy-9-methylphosphono-2-propyl-alpha-D- glycero-D-galacto-nonulopyranosidonic acid triethylammonium salt (2), and 5-acetamido-9-thiomethylmercuric-3, 5,9-trideoxy-beta-D-glycero-D-galacto-nonulopyranosidonic acid (3) were synthesized. Compounds 1 and 2 are proposed transition state inhibitors of an esterase vital for the binding and infection of influenza C. Compound 3 was enzymatically incorporated into an oligosaccharide and a non-natural glycoprotein for use as an aid in the structure determination of these compounds by X-ray crystallography.
Martin
R
R
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Witte
K L
KL
Wong
C H
CH
D000115:Acetylesterase; D002240:Carbohydrate Sequence; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D003568:Cytidine Monophosphate / Q000737:chemistry*; D006001:Glycoconjugates / Q000737:chemistry*; D009982:Gammainfluenzavirus / Q000201:enzymology; D008628:Mercury / Q000737:chemistry*; D008767:Methylmercury Compounds / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D000216:N-Acylneuraminate Cytidylyltransferase / Q000378:metabolism; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D012260:Ribonucleases / Q000378:metabolism; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D012795:Sialoglycoproteins / Q000138:chemical synthesis* / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000378:metabolism; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
C116216:5-acetamido-9-thiomethylmercuric-3,5,9-trideoxy-D-glycero-D-galacto-nonulopyranosidonic acid; C116222:CMP-(5-acetamido-9-thiomethylmercuric-3,5,9-trideoxy-D-glycero-D-galacto-nonulopyranosidonicacid); D006001:Glycoconjugates; D008767:Methylmercury Compounds; D009844:Oligosaccharides; D012794:Sialic Acids; D012795:Sialoglycoproteins; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases; D000216:N-Acylneuraminate Cytidylyltransferase; D012260:Ribonucleases; D002265:Carboxylic Ester Hydrolases; D000115:Acetylesterase; C046298:sialate O-acetylesterase; D003568:Cytidine Monophosphate; D008628:Mercury; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase