Chemoenzymatic Synthesis of a Library of Human Milk Oligosaccharides

作者：Zhongying Xiao, Yuxi Guo, Yunpeng Liu, Lei Li, Qing Zhang, Liuqing Wen, Xuan Wang, Shukkoor Muhammed Kondengaden, Zhigang Wu, Jun Zhou, Xuefeng Cao, Xu Li, Cheng Ma, Peng George Wang · 发表于：The Journal of Organic Chemistry · 年份：2016 · DOI：10.1021/acs.joc.6b00478 · 被引用次数：111 · 研究领域：Infant Nutrition and Health、Carbohydrate Chemistry and Synthesis、Glycosylation and Glycoproteins Research

Human milk oligosaccharides (HMOs) are a family of diverse unconjugated glycans that exist in human milk as one of the major components. Characterization, quantification, and biofunctional studies of HMOs remain a great challenge due to their diversity and complexity. The accessibility of a homogeneous HMO library is essential to solve these issues which have beset academia for several decades. In this study, an efficient chemoenzymatic strategy, namely core synthesis/enzymatic extension (CSEE), for rapid production of diverse HMOs was reported. On the basis of 3 versatile building blocks, 3 core structures were chemically synthesized via consistent use of oligosaccharyl thioether and oligosaccharyl bromide as glycosylation donors in a convergent fragment coupling strategy. Each of these core structures was then extended to up to 11 HMOs by 4 robust glycosyltransferases. A library of 31 HMOs were chemoenzymatically synthesized and characterized by MS and NMR. CSEE indeed provides a practical approach to harvest structurally defined HMOs for various applications.