Synthetic Disialyl Hexasaccharides Protect Neonatal Rats from Necrotizing Enterocolitis

Two novel synthetic a2-6-linked disialyl hexasac- charides, disialyllacto-N-neotetraose (DSLNnT) and a2-6- linked disialyllacto-N-tetraose (DS'LNT), were readily obtained by highly efficient one-pot multienzyme (OPME) reactions. The sequential OPME systems described herein allowed the use of an inexpensive disaccharide and simple monosaccharides to synthesize the desired complex oligosac- charides with high efficiency and selectivity. DSLNnT and DS'LNT were shown to protect neonatal rats from necrotizing enterocolitis (NEC) and are good therapeutic candidates for preclinical experiments and clinical application in treating NEC in preterm infants. Human milk oligosaccharides (HMOS) are a mixture of more than 100 glycans, which constitute the third major component of human milk. (1) They have been found to contribute significantly to the gut health of breastfed infants. Strong evidence is now available to support the roles of HMOS in promoting the growth of beneficial gut bacteria, inhibiting the binding of pathogenic bacteria, human immu- nodeficiency virus (HIV), or protozoan parasites to gut epithelial cells, modulating immune responses, and influenc- ing the functions of the gut epithelium. (2) Most of the reported HMOS-related studies used HMOS