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

Yu, Hai and Yan, Xuebin and Autran, Chloe A. and Li, Yanhong and Etzold, Sabrina and Latasiewicz, Joanna and Robertson, Bianca M. and Li, Jiaming and Bode, Lars and Chen, Xi (2017) Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects. Journal of Organic Chemistry, 82 (24). pp. 13152-13160. ISSN 0022-3263. https://resolver.caltech.edu/CaltechAUTHORS:20171114-150408009

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acs.joc.7b02167DOIArticle
http://pubs.acs.org/doi/10.1021/acs.joc.7b02167PublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/acs.joc.7b02167PublisherSupporting Information
ORCID:
AuthorORCID
Li, Jiaming0000-0001-6646-5693
Chen, Xi0000-0002-3160-614X
Additional Information:© 2017 American Chemical Society. Received: September 4, 2017. Published: November 10, 2017. This work was supported by NIH grants R43HD087077 (to H.Y.) and R01HD065122 (to X.C.) as well as a scholarship from the China Scholarship Council (to X.Y.). The support of the Family Larsson-Rosenquist Foundation (to L.B.) is gratefully acknowledged. The authors declare the following competing financial interest(s): H.Y., Y.L., and X.C. are co-founders of Glycohub, Inc., a company focused on the development of carbohydrate-based reagents, diagnostics, and therapeutics.
Funders:
Funding AgencyGrant Number
NIHR43HD087077
NIHR01HD065122
China Scholarship CouncilUNSPECIFIED
Family Larsson-Rosenquist FoundationUNSPECIFIED
Issue or Number:24
Record Number:CaltechAUTHORS:20171114-150408009
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20171114-150408009
Official Citation: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, and Xi Chen. The Journal of Organic Chemistry 2017 82 (24), 13152-13160 DOI: 10.1021/acs.joc.7b02167
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:83203
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 Nov 2017 23:11
Last Modified:03 Oct 2019 19:03

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