Chemo-enzymatic synthesis of Neu5Gc-containing sialylated lactulose

Abstract

Purpose: To synthesize novel sialylated lactuloses, namely, Neu5Gc-α2,3-lactulose and Neu5Gc-α2,6-lactulose. Methods: ManNGc was chemically synthesized from commercially available N-acetylmannosaime (ManNAc), which was used as the donor substrate to synthesize α-(2→3) linkage and α-(2→6) linkage sialyllactulose from lactulose via sialyltransferases-catalyzed one-pot multienzyme (OPME) approach. The sialylated products were purified by silica gel flash chromatography column. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to confirm the purity and characterize the structure of the new compounds. Results: Sialyllactulose with α-(2→3) linkage (Neu5Gc-α2,3-lactulose) and α-(2→6) linkage (Neu5Gc-α2,6-lactulose) were efficiently synthesized by an efficient one-pot multienzyme sialylation approach from ManNGc, sodium pyruvate, CTP, and lactulose. The molecular weight of the two products, based on mass spectral data was 648 Da while NMR data indicated the formation of sialylated glycans. Conclusion: Novel sialylated oligosaccharides have been efficiently synthesized from lactulose using highly efficient OPME sialylation approaches. Further investigations are required to ascertain the probiotic activities for possible applications in pharmaceutical and food industries.