Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects

Hai Yu, Xuebin Yan, Chloe A. Autran, Yanhong Li, Sabrina Etzold, Joanna Latasiewicz, Bianca M. Robertson, Jiaming Li, Lars Bode, Xi Chen

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Necrotizing enterocolitis (NEC) is one of the most common and devastating intestinal disorders in preterm infants. Therapies to meet the clinical needs for this special and highly vulnerable population are extremely limited. A specific human milk oligosaccharide (HMO), disialyllacto-N-tetraose (DSLNT), was shown to contribute to the beneficial effects of breastfeeding as it prevented NEC in a neonatal rat model and was associated with lower NEC risk in a human clinical cohort study. Herein, gram-scale synthesis of two DSLNT analogs previously shown to have NEC preventing effect is described. In addition, four novel disialyl glycans have been designed and synthesized by enzymatic or chemoenzymatic methods. Noticeably, two disialyl tetraoses have been produced by enzymatic sialylation of chemically synthesized thioethyl β-disaccharides followed by removal of the thioethyl aglycon. Dose-dependent and single-dose comparison studies showed varying NEC-preventing effects of the disialyl glycans in neonatal rats. This study helps to refine the structure requirement of the NEC-preventing effect of disialyl glycans and provides important dose-dependent information for using DSLNT analogs as potential therapeutics for NEC prevention in preterm infants.

Original languageEnglish (US)
Pages (from-to)13152-13160
Number of pages9
JournalJournal of Organic Chemistry
Volume82
Issue number24
DOIs
StatePublished - Dec 15 2017

ASJC Scopus subject areas

  • Organic Chemistry

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    Yu, H., Yan, X., Autran, C. A., Li, Y., Etzold, S., Latasiewicz, J., Robertson, B. M., Li, J., Bode, L., & Chen, X. (2017). Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects. Journal of Organic Chemistry, 82(24), 13152-13160. https://doi.org/10.1021/acs.joc.7b02167