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

18 Citations (Scopus)

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

Fingerprint

Polysaccharides
Rats
Disaccharides
Oligosaccharides
disialyllacto-N-tetraose
Human Milk

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects. / Yu, Hai; Yan, Xuebin; Autran, Chloe A.; Li, Yanhong; Etzold, Sabrina; Latasiewicz, Joanna; Robertson, Bianca M.; Li, Jiaming; Bode, Lars; Chen, Xi.

In: Journal of Organic Chemistry, Vol. 82, No. 24, 15.12.2017, p. 13152-13160.

Research output: Contribution to journalArticle

Yu, H, Yan, X, Autran, CA, Li, Y, Etzold, S, Latasiewicz, J, Robertson, BM, Li, J, Bode, L & Chen, X 2017, 'Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects', Journal of Organic Chemistry, vol. 82, no. 24, pp. 13152-13160. https://doi.org/10.1021/acs.joc.7b02167
Yu, Hai ; Yan, Xuebin ; Autran, Chloe A. ; Li, Yanhong ; Etzold, Sabrina ; Latasiewicz, Joanna ; Robertson, Bianca M. ; Li, Jiaming ; Bode, Lars ; Chen, Xi. / Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects. In: Journal of Organic Chemistry. 2017 ; Vol. 82, No. 24. pp. 13152-13160.
@article{c12cd7c2ee4641b5a2776f226bf58f2a,
title = "Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects",
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.",
author = "Hai Yu and Xuebin Yan and Autran, {Chloe A.} and Yanhong Li and Sabrina Etzold and Joanna Latasiewicz and Robertson, {Bianca M.} and Jiaming Li and Lars Bode and Xi Chen",
year = "2017",
month = "12",
day = "15",
doi = "10.1021/acs.joc.7b02167",
language = "English (US)",
volume = "82",
pages = "13152--13160",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "24",

}

TY - JOUR

T1 - Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects

AU - Yu, Hai

AU - Yan, Xuebin

AU - Autran, Chloe A.

AU - Li, Yanhong

AU - Etzold, Sabrina

AU - Latasiewicz, Joanna

AU - Robertson, Bianca M.

AU - Li, Jiaming

AU - Bode, Lars

AU - Chen, Xi

PY - 2017/12/15

Y1 - 2017/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85038436582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038436582&partnerID=8YFLogxK

U2 - 10.1021/acs.joc.7b02167

DO - 10.1021/acs.joc.7b02167

M3 - Article

C2 - 29124935

AN - SCOPUS:85038436582

VL - 82

SP - 13152

EP - 13160

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 24

ER -