Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly.

The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Here, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides as minimal precursors rather than monosaccharides greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the 'sulfation code' and understanding the roles of specific GAG structures in physiology and disease.

[1]  P. Azadi,et al.  N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization , 2019, Nature Communications.

[2]  L. Troeberg,et al.  Heparan sulfate as a regulator of inflammation and immunity , 2018, Journal of leukocyte biology.

[3]  U. Desai,et al.  Sulfotransferase and Heparanase: Remodeling Engines in Promoting Virus Infection and Disease Development , 2018, Front. Pharmacol..

[4]  Kenji F. Tanaka,et al.  Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships , 2018, Cell.

[5]  Chi-Huey Wong,et al.  Programmable one-pot synthesis of heparin pentasaccharides enabling access to regiodefined sulfate derivatives† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc01743c , 2018, Chemical science.

[6]  Salvatore G. Pistorio,et al.  Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges. , 2018, Chemical reviews.

[7]  R. Sanderson,et al.  Opposing Functions of Heparanase-1 and Heparanase-2 in Cancer Progression. , 2018, Trends in biochemical sciences.

[8]  S. Hung,et al.  Synthetic heparin and heparan sulfate: probes in defining biological functions. , 2017, Current opinion in chemical biology.

[9]  R. Linhardt,et al.  Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Heparins With Enoxaparin , 2017, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[10]  T. Handel,et al.  Heparan Sulfate Microarray Reveals That Heparan Sulfate-Protein Binding Exhibits Different Ligand Requirements. , 2017, Journal of the American Chemical Society.

[11]  R. Heilbronn,et al.  Automated Glycan Assembly of Oligo-N-Acetyllactosamine and Keratan Sulfate Probes to Study Virus-Glycan Interactions , 2017 .

[12]  N. Moitessier,et al.  Regioselective acylation, alkylation, silylation and glycosylation of monosaccharides , 2016 .

[13]  M. Ishihara,et al.  Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1. , 2016, Journal of the American Chemical Society.

[14]  U. Schepers,et al.  Chemical Synthesis of Glycosaminoglycans. , 2016, Chemical reviews.

[15]  E. Krenske,et al.  The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-D-glucuronides to L-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations. , 2016, Organic & biomolecular chemistry.

[16]  Jie Shen,et al.  Direct C5-Isomerization Approach to l-Iduronic Acid Derivatives , 2015 .

[17]  P. Wang,et al.  Facile chemoenzymatic synthesis of biotinylated heparosan hexasaccharide. , 2015, Organic & biomolecular chemistry.

[18]  G. Jayson,et al.  Synthesis of L-iduronic acid derivatives via [3.2.1] and [2.2.2] L-iduronic lactones from bulk glucose-derived cyanohydrin hydrolysis: a reversible conformationally switched superdisarmed/rearmed lactone route to heparin disaccharides. , 2015, The Journal of organic chemistry.

[19]  Alexei V. Demchenko,et al.  Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry , 2015, Chemical science.

[20]  J. Esko,et al.  Demystifying heparan sulfate-protein interactions. , 2014, Annual review of biochemistry.

[21]  Yanhong Li,et al.  Tailored design and synthesis of heparan sulfate oligosaccharide analogues using sequential one-pot multienzyme systems. , 2013, Angewandte Chemie.

[22]  G. Jayson,et al.  Tetrasaccharide iteration synthesis of a heparin-like dodecasaccharide and radiolabelling for in vivo tissue distribution studies , 2013, Nature Communications.

[23]  L. Kjellén,et al.  Pathophysiology of heparan sulphate: many diseases, few drugs , 2013, Journal of internal medicine.

[24]  S. Hung,et al.  Divergent synthesis of 48 heparan sulfate-based disaccharides and probing the specific sugar-fibroblast growth factor-1 interaction. , 2012, Journal of the American Chemical Society.

[25]  Xuefei Huang,et al.  Chemical synthesis of a heparan sulfate glycopeptide: syndecan-1. , 2012, Angewandte Chemie.

[26]  S. Mousa,et al.  Chemoenzymatic Synthesis of Homogeneous Ultralow Molecular Weight Heparins , 2011, Science.

[27]  S. Hung,et al.  Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction. , 2011, Nature chemistry.

[28]  R. Linhardt,et al.  E. coli K5 fermentation and the preparation of heparosan, a bioengineered heparin precursor , 2010, Biotechnology and bioengineering.

[29]  Eun-Ho Song,et al.  Synthesis of multivalent tuberculosis and Leishmania-associated capping carbohydrates reveals structure-dependent responses allowing immune evasion. , 2010, Journal of the American Chemical Society.

[30]  H. Lortat-Jacob,et al.  The molecular basis and functional implications of chemokine interactions with heparan sulphate. , 2009, Current opinion in structural biology.

[31]  G. Jayson,et al.  Scalable synthesis of L-iduronic acid derivatives via stereocontrolled cyanohydrin reaction for synthesis of heparin-related disaccharides. , 2009, Organic letters.

[32]  Joseph Zaia,et al.  Organ-specific Heparan Sulfate Structural Phenotypes* , 2009, Journal of Biological Chemistry.

[33]  H. Kitagawa,et al.  Heparan sulphate biosynthesis and disease. , 2008, Journal of biochemistry.

[34]  J. Jacquinet,et al.  From polymer to size-defined oligomers: an expeditious route for the preparation of chondroitin oligosaccharides. , 2006, Angewandte Chemie.

[35]  L. Hsieh‐Wilson,et al.  Chemical approaches to deciphering the glycosaminoglycan code. , 2005, Current opinion in chemical biology.

[36]  H. Overkleeft,et al.  A modular strategy toward the synthesis of heparin-like oligosaccharides using monomeric building blocks in a sequential glycosylation strategy. , 2005, Journal of the American Chemical Society.

[37]  Maurice Petitou,et al.  Ein synthetisches Antithrombin III bindendes Pentasaccharid ist jetzt ein Wirkstoff! Was kommt danach? , 2004 .

[38]  C. V. van Boeckel,et al.  A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? , 2004, Angewandte Chemie.

[39]  Chi‐Huey Wong,et al.  Novel efficient routes to heparin monosaccharides and disaccharides achieved via regio- and stereoselective glycosidation. , 2004, Organic letters.

[40]  J. D. de Paz,et al.  Synthesis of heparin-like oligosaccharides on a soluble polymer support. , 2003, Chemical communications.

[41]  G. Boons,et al.  New set of orthogonal protecting groups for the modular synthesis of heparan sulfate fragments. , 2003, Organic letters.

[42]  P. Seeberger,et al.  Modular synthesis of heparin oligosaccharides. , 2003, Chemistry.

[43]  R. Linhardt,et al.  Heparin‐Protein‐Wechselwirkungen , 2002 .

[44]  R. Linhardt,et al.  Heparin-protein interactions. , 2002, Angewandte Chemie.

[45]  Jian Liu,et al.  Cell surface heparan sulfate and its roles in assisting viral infections , 2002, Medicinal research reviews.

[46]  M. Salmivirta,et al.  Age-dependent Modulation of Heparan Sulfate Structure and Function* , 1998, The Journal of Biological Chemistry.

[47]  J. Turnbull,et al.  Structural Modification of Fibroblast Growth Factor-binding Heparan Sulfate at a Determinative Stage of Neural Development* , 1998, The Journal of Biological Chemistry.

[48]  D. Medaković.  An Efficient Synthesis of Methyl 1,2,3,4‐Tetra‐O‐acetyl‐β‐L‐ idopyranuronate. , 1994 .

[49]  T. Chiba,et al.  Application of a radical reaction to the synthesis of l-iduronic acid derivatives from d-glucuronic acid analogues☆ , 1986 .

[50]  S. Hanessian,et al.  Regioselective manipulation of hydroxyl groups via organotin derivatives , 1985 .

[51]  J. Shively,et al.  Formation of anhydrosugars in the chemical depolymerization of heparin. , 1976, Biochemistry.

[52]  J. J. Carr,et al.  Investigations on the chemistry of heparin. I. Desulfation and acetylation. , 1960, Archives of biochemistry and biophysics.

[53]  E. Davidson,et al.  Structural Studies on Chondroitin Sulfuric Acid.1,2 I. The Nature of Chondrosine , 1954 .