Facile Chemoenzymatic Synthesis of O‐Mannosyl Glycans

Wang, Shuaishuai; Zhang, Qing; Chen, Congcong; Guo, Yuxi; Gadi, Madhusudhan Reddy; Yu, Jin; Westerlind, Ulrika; Liu, Yunpeng; Cao, Xuefeng; Wang, Peng George; Li, Lei

doi:10.1002/anie.201803536

Cited by 33 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2a ), we designed three synthetic building blocks, including a versatile protected glycosyl amino acid 7 with C3-OH protected by an acetyl (Ac) group and C4/6-OH masked by a benzylidene acetal, and two monosaccharide Schmidt donors 8 30 and 9 31 . The Fmoc group is introduced to the Ser residue of 7 to facilitate reaction monitoring and product purification 32 . The Ac group on 7 would be selectively removed under mild basic conditions.…”

Section: Resultsmentioning

confidence: 99%

“…However, despite maintaining the pH of the reaction below 8.5 during Zemplén deprotection, nearly 50% of Fmoc was lost. Fmoc was therefore quantitavely reintroduced under basic conditions using Fmoc N -hydroxysuccinimide ester before product purification 32 . Core 2 ( 2 ) was obtained with a yield of 77% over the last three steps.…”

Section: Resultsmentioning

confidence: 99%

“…Extensive efforts have also been made on evaluating structural modification of sugar donors with various protective groups [36][37][38][39] , leaving groups 40 , and reaction conditions 41,42 . For the purpose of preparing structurally diverse O-GalNAc glycans, a simple, efficient, and diversity-oriented route encompassing a fluorescent core (e.g., Fmoc) would be more advantageous 32 . A stable thio glycosyl donor 10 43 was thus selected and obtained by efficient synthetic methods 44 .…”

Section: Symbolmentioning

confidence: 99%

See 2 more Smart Citations

Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics

et al. 2021

Self Cite

View full text Add to dashboard Cite

O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression. Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds. Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans. The key to this strategy is the convergent assembly of O-GalNAc cores 1–4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules. A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray. Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics. Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Symbolmentioning

confidence: 99%

See 1 more Smart Citation

Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Reactions generally proceed under mild, aqueous conditions without the need for toxic and harsh organic reagents. Using bio- and/or chemoenzymatic synthesis tools, several natural and engineered glycan libraries have recently been constructed including asymmetric multi-antennary N -glycans (Wang Z. et al, 2013 ), glycosphingolipid glycans (Yu et al, 2016 ), authentic human type N -glycans (Li L. et al, 2015 ; Hamilton et al, 2017 ), O -mannosyl glycans (Meng et al, 2018 ; Wang S. et al, 2018 ), human milk oligosaccharides (HMOs) (Xiao et al, 2016 ; Prudden et al, 2017 ), and tumor-associated antigens (Li P. J. et al, 2019 ; 'T Hart et al, 2019 ). Similar strategies have been adopted for cell-free enzymatic synthesis of glycolipid libraries including those from bacterial (Glover K. et al, 2005 ), animal (Stubs et al, 2010 ), and human origins (Li S. T. et al, 2019 ).…”

Section: Enzyme-mediated In Vitro Technologies Formentioning

confidence: 99%

Cell-Free Synthetic Glycobiology: Designing and Engineering Glycomolecules Outside of Living Cells

Jaroentomeechai

Taw

et al. 2020

Front. Chem.

View full text Add to dashboard Cite

Glycans and glycosylated biomolecules are directly involved in almost every biological process as well as the etiology of most major diseases. Hence, glycoscience knowledge is essential to efforts aimed at addressing fundamental challenges in understanding and improving human health, protecting the environment and enhancing energy security, and developing renewable and sustainable resources that can serve as the source of next-generation materials. While much progress has been made, there remains an urgent need for new tools that can overexpress structurally uniform glycans and glycoconjugates in the quantities needed for characterization and that can be used to mechanistically dissect the enzymatic reactions and multi-enzyme assembly lines that promote their construction. To address this technology gap, cell-free synthetic glycobiology has emerged as a simplified and highly modular framework to investigate, prototype, and engineer pathways for glycan biosynthesis and biomolecule glycosylation outside the confines of living cells. From nucleotide sugars to complex glycoproteins, we summarize here recent efforts that harness the power of cell-free approaches to design, build, test, and utilize glyco-enzyme reaction networks that produce desired glycomolecules in a predictable and controllable manner. We also highlight novel cell-free methods for shedding light on poorly understood aspects of diverse glycosylation processes and engineering these processes toward desired outcomes. Taken together, cell-free synthetic glycobiology represents a promising set of tools and techniques for accelerating basic glycoscience research (e.g., deciphering the “glycan code”) and its application (e.g., biomanufacturing high-value glycomolecules on demand).

show abstract

“…Chemo-enzymatic approaches have been developed for the synthesis of structurally defined glycans in the last two decades (Koeller et al, 2000 ; Blixt and Razi, 2006 ; Boltje et al, 2009 ; Lepenies et al, 2010 ; Palcic, 2011 ; Schmaltz et al, 2011 ). A lot of effort and various synthetic methods have been introduced to make more complex glycans available (Wang et al, 2013 , 2018 ; Chen, 2015 ; Li et al, 2015 ; Shivatare et al, 2016 ; Prudden et al, 2017 ; Zhang et al, 2017 ; Wen et al, 2018 ; Liu et al, 2019 ), and recently, two enzyme-mediated oligosaccharide synthesizers were reported to facilitate the synthetic progress (Zhang et al, 2018 ; Li et al, 2019 ). Despite many recent advancements in prototypic automated glycan synthesis, the synthesis of complex, highly branched glycan structures is still extremely challenging and can only be carried out in a number of noncommercialized laboratories.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Complex Glycans From Natural Sources for Functional Study

Zhang

Song

2020

Front. Chem.

Self Cite

View full text Add to dashboard Cite

One major barrier in glycoscience is the lack of diverse and biomedically relevant complex glycans in sufficient quantities for functional study. Complex glycans from natural sources serve as an important source of these glycans and an alternative to challenging chemoenzymatic synthesis. This review discusses preparation of complex glycans from several classes of glycoconjugates using both enzymatic and chemical release approaches. Novel technologies have been developed to advance the large-scale preparation of complex glycans from natural sources. We also highlight recent approaches and methods developed in functional and fluorescent tagging and high-performance liquid chromatography (HPLC) isolation of released glycans.

show abstract

Facile Chemoenzymatic Synthesis of O‐Mannosyl Glycans

Cited by 33 publications

References 31 publications

Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics

Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics

Cell-Free Synthetic Glycobiology: Designing and Engineering Glycomolecules Outside of Living Cells

Preparation of Complex Glycans From Natural Sources for Functional Study

Contact Info

Product

Resources

About