Reversible O-Acetyl Migration within the Sialic Acid Side Chain and Its Influence on Protein Recognition

Yang Ji, Aniruddha Sasmal, Wanqing Li, Lisa Oh, Saurabh Srivastava, Audra A. Hargett, Brian R. Wasik, Hai Yu, Sandra Diaz, Biswa Choudhury, Colin R. Parrish, Darón I. Freedberg, Lee Ping Wang, Ajit Varki, Xi Chen

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

O-Acetylation is a common naturally occurring modification of carbohydrates and is especially widespread in sialic acids, a family of nine-carbon acidic monosaccharides. O-Acetyl migration within the exocyclic glycerol-like side chain of mono-O-acetylated sialic acid reported previously was from the C7- to C9-hydroxyl group with or without an 8-O-acetyl intermediate, which resulted in an equilibrium that favors the formation of the 9-O-acetyl sialic acid. Herein, we provide direct experimental evidence demonstrating that O-acetyl migration is bidirectional, and the rate of equilibration is influenced predominantly by the pH of the sample. While the O-acetyl group on sialic acids and sialoglycans is stable under mildly acidic conditions (pH < 5, the rate of O-acetyl migration is extremely low), reversible O-acetyl migration is observed readily at neutral pH and becomes more significant when the pH increases to slightly basic. Sialoglycan microarray studies showed that esterase-inactivated porcine torovirus hemagglutinin-esterase bound strongly to sialoglycans containing a more stable 9-N-acetylated sialic acid analog, but these compounds were less resistant to periodate oxidation treatment compared to their 9-O-acetyl counterparts. Together with prior studies, the results support the possible influence of sialic acid O-acetylation and O-acetyl migration to host-microbe interactions and potential application of the more stable synthetic N-acetyl mimics.

Original languageEnglish (US)
JournalACS Chemical Biology
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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