Chemoenzymatic Synthesis of a Library of Human Milk Oligosaccharides.
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.
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Zhongying
Z
Xiao
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Yuxi
Y
Guo
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Yunpeng
Y
Liu
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Lei
L
Li
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Qing
Q
Zhang
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Liuqing
L
Wen
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Xuan
X
Wang
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Shukkoor Muhammed
SM
Kondengaden
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Zhigang
Z
Wu
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Jun
J
Zhou
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Xuefeng
X
Cao
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Xu
X
Li
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Cheng
C
Ma
Department of Chemistry and Center of Diagnostics & Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Peng George
PG
Wang
D001965:Bromides / Q000737:chemistry; D002625:Chemistry, Organic; D002851:Chromatography, High Pressure Liquid; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis*; D011134:Polysaccharides / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013440:Sulfides / Q000737:chemistry
D001965:Bromides; D009844:Oligosaccharides; D011134:Polysaccharides; D013440:Sulfides; D016695:Glycosyltransferases