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

Autor: Yu H; Glycohub, Inc. , 4070 Truxel Road, Sacramento, California 95834, United States.; Department of Chemistry, University of California , One Shields Avenue, Davis, California 95616, United States., Yan X; Department of Chemistry, University of California , One Shields Avenue, Davis, California 95616, United States.; College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou, Henan 450001, China., Autran CA; Division of Neonatology and Division of Gastroenterology and Nutrition, Department of Pediatrics, and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (LRF MoMI CoRE), University of California-San Diego , La Jolla, California 92093, United States., Li Y; Glycohub, Inc. , 4070 Truxel Road, Sacramento, California 95834, United States.; Department of Chemistry, University of California , One Shields Avenue, Davis, California 95616, United States., Etzold S; Division of Neonatology and Division of Gastroenterology and Nutrition, Department of Pediatrics, and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (LRF MoMI CoRE), University of California-San Diego , La Jolla, California 92093, United States., Latasiewicz J; Division of Neonatology and Division of Gastroenterology and Nutrition, Department of Pediatrics, and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (LRF MoMI CoRE), University of California-San Diego , La Jolla, California 92093, United States., Robertson BM; Division of Neonatology and Division of Gastroenterology and Nutrition, Department of Pediatrics, and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (LRF MoMI CoRE), University of California-San Diego , La Jolla, California 92093, United States., Li J; Department of Chemistry, University of California , One Shields Avenue, Davis, California 95616, United States.; Department of Chemistry, Zhejiang University , Hangzhou, Zhejiang 310027, China., Bode L; Division of Neonatology and Division of Gastroenterology and Nutrition, Department of Pediatrics, and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (LRF MoMI CoRE), University of California-San Diego , La Jolla, California 92093, United States., Chen X; Department of Chemistry, University of California , One Shields Avenue, Davis, California 95616, United States.
Jazyk: angličtina
Zdroj: The Journal of organic chemistry [J Org Chem] 2017 Dec 15; Vol. 82 (24), pp. 13152-13160. Date of Electronic Publication: 2017 Nov 22.
DOI: 10.1021/acs.joc.7b02167
Abstrakt: 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.
Databáze: MEDLINE