One-pot synthesis of N-acetyl- and N-glycolylneuraminic acid capped trisaccharides and evaluation of their influenza A(H1 N1) inhibition.
Human lung epithelial cells natively offer terminal N-acetylneuraminic acid (Neu5Ac) α(2→6)-linked to galactose (Gal) as binding sites for influenza virus hemagglutinin. N-Glycolylneuraminic acid (Neu5Gc) in place of Neu5Ac is known to affect hemagglutinin binding in other species. Not normally generated by humans, Neu5Gc may find its way to human cells from dietary sources. To compare their influence in influenza virus infection, six trisaccharides with Neu5Ac or Neu5Gc α(2→6) linked to Gal and with different reducing end sugar units were prepared using one-pot assembly and divergent transformation. The sugar assembly made use of an N-phthaloyl-protected sialyl imidate for chemoselective activation and α-stereoselective coupling with a thiogalactoside. Assessment of cytopathic effect showed that the Neu5Gc-capped trisaccharides inhibited the viral infection better than their Neu5Ac counterparts.
Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Taipei 115 (Taiwan); Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 300 (Taiwan).
Yun
Y
Hsu
Hsiu-Hwa
HH
Ma
Larry S
LS
Lico
Jia-Tsrong
JT
Jan
Koichi
K
Fukase
Yosuke
Y
Uchinashi
Medel Manuel L
MM
Zulueta
Shang-Cheng
SC
Hung
D000107:Acetylation; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy; D009438:Neuraminic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D014312:Trisaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000998:Antiviral Agents; D009438:Neuraminic Acids; D014312:Trisaccharides; C032592:N-glycolylneuraminic acid
carbohydrates; glycosylation; stereoselectivity; synthetic methods; viruses