- Immunological response from an entirely carbohydrate antigen: Design of synthetic vaccines based on Tn-PS A1 conjugates
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(Figure Presented) An entirely carbohydrate-based immunogen consisting of a zwitterionic polysaccharide (ZPS) PS A1 and the well-known tumor antigen Tn has been designed, synthesized, and studied for immunological effects. The PS A1 motif was included to act as an MHCII elicitor for a T-cell-dependent immune response with increased immunogenicity against tumor-associated carbohydrate antigens, providing an alternative to carrier proteins. Through the use of C57BL/6 mice, it has been shown that chemical modification of PS A1 does not alter the recognition sequence responsible for an MHCII-mediated, T-cell-dependent immune response. The Tn-PS A1 conjugate construct confers specificity toward the Tn antigen alone, and specific carbohydrate immunoglobulins, namely, IgG3, are generated from intraperitoneal immunizations with or without adjuvant. The properties of the vaccine candidate are attributed to a site-specific linking strategy that incurs significant incorporation of Tn antigen.
- De Silva, Ravindra A.,Wang, Qianli,Chidley, Tristan,Appulage, Dananjaya K.,Andreana, Peter R.
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Read Online
- Safe and Scalable Continuous Flow Azidophenylselenylation of Galactal to Prepare Galactosamine Building Blocks
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Differentially protected galactosamine building blocks are key components for the synthesis of human and bacterial oligosaccharides. The azidophenylselenylation of 3,4,6-tri-O-acetyl-d-galactal provides straightforward access to the corresponding 2-nitrog
- Guberman, Mónica,Pieber, Bartholom?us,Seeberger, Peter H.
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supporting information
p. 2764 - 2770
(2019/12/24)
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- Synthesis of trisaccharide repeating unit of fucosylated chondroitin sulfate
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We described the chemical synthesis of a sulfated trisaccharide repeating unit of fucosylated chondroitin sulfate (FCS), which has significant anticoagulant activity. Well-functionalized monosaccharides were readily prepared, and highly efficient glycosyl
- He, Haiqing,Chen, Dong,Li, Xiaomei,Li, Chengji,Zhao, Jin-Hua,Qin, Hong-Bo
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p. 2877 - 2882
(2019/03/21)
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- A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine
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Synthetic approaches towards N-acetylgalactosamine (GalNAc) have been attracting considerable interest since this compound is known for its pivotal role in cell-cell interaction and receptor induced cell signaling. Herein, we present a synthetic route in which two of the four stereogenic centers present in the target compound are derived from enantiopure tartaric acid being selectively converted to epoxy alcohols. The key step is the Pd-catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc).
- Riedl, Bettina,Schmid, Walther
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p. 856 - 860
(2018/04/30)
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- Synthetic and immunological studies on trimeric MUC1 immunodominant motif antigen-based anti-cancer vaccine candidates
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Therapeutic vaccines have been regarded as a very promising treatment modality against cancer. Tumor-associated MUC1 is a promising antigen for the design of antitumor vaccines. However, body's immune tolerance and low immunogenicity of MUC1 glycopeptides
- Li, Mingjing,Yu, Fan,Yao, Chao,Wang, Peng George,Liu, Yonghui,Zhao, Wei
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p. 993 - 999
(2018/02/19)
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- A Modular Approach to the Total Synthesis of Tunicamycins
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The tunicamycins constitute a delicate mimic of the bisubstrate intermediates of N-acetyl-D-hexosamine-1-phosphate translocases and thus inhibit bacterial cell-wall synthesis and the N glycosylation of eukaryotic proteins. An efficient approach to the synthesis of this unique type of nucleoside antibiotics is now reported and features the assembly of five modules in a highly stereoselective and robust manner. A Mukaiyama aldol reaction, intramolecular acetal formation, gold(I)-catalyzed O and N glycosylation, and final Nacylation were used as the key steps. The modular and stereoselective synthesis of tunicamycins features a Mukaiyama aldol reaction, intramolecular acetal formation, gold(I)-catalyzed O and N glycosylation, and final N acylation as the key steps. These natural products are a unique type of nucleoside antibiotics with potent inhibitory activities against bacterial cell-wall synthesis and the N-glycosylation of eukaryotic proteins.
- Li, Jiakun,Yu, Biao
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supporting information
p. 6618 - 6621
(2015/06/08)
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- Cytotoxic properties of d-gluco-, d-galacto- and d-manno-configured 2-amino-2-deoxy-glycerolipids against epithelial cancer cell lines and BT-474 breast cancer stem cells
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Glycosylated antitumor ether lipids (GAELs) 6 and 7 containing a α- or β-d-gluco-configured 2-amino-2-deoxy (2-NH2-Glc) sugar moiety linked to a glycerolipid aglycone kill cancer cell lines via a non-apoptotic mechanism that could be exploited
- Samadder, Pranati,Xu, Yaozu,Schweizer, Frank,Arthur, Gilbert
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p. 225 - 235
(2014/04/17)
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- Synthesis of peptides and glycopeptides with polyproline II helical topology as potential antifreeze molecules
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A library of peptides and glycopeptides containing (4R)-hydroxy-l-proline (Hyp) residues were designed with a view to providing stable polyproline II (PPII) helical molecules with antifreeze activity. A library of dodecapeptides containing contiguous Hyp
- Corcilius, Leo,Santhakumar, Gajan,Stone, Robin S.,Capicciotti, Chantelle J.,Joseph, Soumya,Matthews, Jacqueline M.,Ben, Robert N.,Payne, Richard J.
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p. 3569 - 3581
(2013/07/05)
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- Synthesis of an isotopically-labelled antarctic fish antifreeze glycoprotein probe
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Antifreeze glycoproteins (AFGPs) are glycosylated polypeptides produced by Antarctic and Arctic fishes, which allow them to survive in seawater at sub-zero temperatures. An investigation into the postulated enteric uptake of AFGP synthesized in the exocrine pancreas of Antarctic fishes required a custom-prepared AFGP probe that incorporated seven isotopically-labelled Ala residues for detection by mass spectrometry. The AFGPs are composed of a repetitive three amino acid unit (Ala-Ala-Thr), in which the threonine residue is glycosylated with the disaccharide β-d-Gal-(1→3) α-d-GalNAc. The synthesis of isotopically-labelled AFGP8 (1), as well as the optimized synthesis of the protected glycosylated amino acid building block 2, is reported.
- Wojnar, Joanna M.,Evans, Clive W.,Devries, Arthur L.,Brimble, Margaret A.
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p. 723 - 731
(2012/07/14)
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- Microwave-assisted synthesis of fluorescein-labelled GalNAcα1-O-Ser/ Thr (Tn) glycopeptides as immunological probes
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Fluorescently labelled glycopeptides containing GalNAcα1-O-Ser/Thr residues provide valuable immunological probes for the development of cancer vaccines. The microwave-assisted automated Fmoc solid-phase synthesis of a series of 5(6)-carboxyfluorescein-labelled GalNAcα1-O-Ser/Thr peptides is described. Lys(Dde)-Gly-Wang polystyrene resin was elongated using Fmoc SPPS with incorporation of several GalNAcα1-O-Ser/Thr residues. Deprotection of the Lys(Dde) then allowed attachment of the 5(6)-carboxyfluorescein label. The synthetic methodology described is flexible and suitably robust enabling the incorporation of three contiguous GalNAcα1-O-Ser residues into the peptide chain. Georg Thieme Verlag Stuttgart · New York.
- Lee, Dong Jun,Harris, Paul W.R.,Kowalczyk, Renata,Dunbar, P. Rod,Brimble, Margaret A.
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experimental part
p. 763 - 769
(2010/10/01)
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- Cowpea mosaic virus capsid: A promising carrier for the development of carbohydrate based antitumor vaccines
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Immunotherapy targeting tumor cell surface carbohydrates is a promising approach for cancer treatment. However, the low immunogenecity of carbohydrates presents a formidable challenge. We describe here the enhancement of carbohydrate immunogenicity by an ordered display on the surface of the cowpea mosaic virus (CPMV) capsid. The Tn glycan, which is overexpressed on numerous cancer cell surfaces, was selected as the model antigen for our study. Previously it has been shown that it is difficult to induce a strong T cell-dependent immune response against the monomeric form of Tn presented in several ways on differeent carriers. In this study, we first synthesized Tn antigens derivatized with either a maleimide or a bromoacetamide moiety that was conjugated selectively to a cysteine mutant of CPMV. The glycoconjugate was then injected into mice and pre- and post-immune antibody levels in the mice sera were measured by enzyme-linked immunosorbant assays. High total antibody titers and, more importantly, high IgG titers specific for Tn were obtained in the post-immune day 35 serum, suggesting the induction of T cell-dependent antibody isotype switching by the glycoconjugate. The antibodies generated were able to recognize Tn antigens presented in their native conformations on the surfaces of both MCF-7 breast cancer cells and the multidrug resistant breast cancer cell line NCI-ADR RES. These results suggest that the CPMV capsid can greatly enhance the immunogenicity of weak antigens such as Tn and this can provide a promising tool for the development of carbohydrate based anti-cancer vaccines.
- Miermont, Adeline,Barnhill, Hannah,Strable, Erica,Lu, Xiaowei,Wall, Katherine A.,Wang, Qian,Finn,Huang, Xuefei
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supporting information; experimental part
p. 4939 - 4947
(2009/04/21)
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- A NOVEL CLASS OF GLYCOSYL DONORS: ANOMERIC S-XANTHATES OF 2-AZIDO-2-DEOXY-D-GALACTOPYRANOSYL DERIVATIVES
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Variously substituted O-ethyl S-(2-azido-2-deoxy-D-galactopyranosyl) dithiocarbonates have been easily prepared via a two-step azidoxanthation reaction of the corresponding galactals (1,5-anhydro-2-deoxy-D-lyxo-hex-1-enitols).They are efficient glycosyl d
- Marra, Alberto,Gauffeny, Francoise,Sinay, Pierre
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p. 5149 - 5160
(2007/10/02)
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- Azidochlorination and diazidization of glycals
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The invention describes a one-pot single step procedure for the azidochlorination or diazidization of glycals, including glycal elements of carbohydrates. Compounds such as 3,4,6-tri-O-benzyl-2-azido-2-deoxy-alpha-D-galactopyranosy chloride, and 3,4,6-tri
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- ADDITION OF HALOGENOAZIDES TO GLYCALS
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Addition of chloroazide to 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-lyxo- (1) and -D-arabino-hex-1-enitol (2) under u.v. irradiation proceeds regio- and stereo-selectively yielding mainly O-acetyl derivatives of 2-azido-2-deoxy-D-galactopyranose and -D-glucopyranose, respectively. 3,4,6-Tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl azide and 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-talopyranose (from 1), and 1,3,4,6-tetra-O-acetyl-2-chloro-2-deoxy-α-D-glucopyranosyl azide and 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-α-D-mannopyranose (from 2) are byproducts. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-D-lyxo- and -D-arabino-hex-1-enitol reacted more rapidly with chloroazide, to give, under irradiation, derivatives of 2-azido-2-deoxy-D-galactose and -D-glucose, respectively.However, reaction in the dark gave mainly O-benzyl derivatives of 2-chloro-2-deoxy-α-D-galacto- and -α-D-glucopyranosyl azide.The difference between the products obtained may depend on the existence of two parallel processes, one radical (under irradiation), and the other ionic (reaction in the dark).
- Bovin, Nicolai V.,Zurabyan, Sergei E.,Khorlin, Anatoly Y.
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- Synthesis of 2-amino-2-deoxyglycoses and 2-amino-2-deoxyglycosides from glycals
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O-acetylated glycals react with ceric ammonium nitrate in the presence of sodium azide to provide, in good yield, O-acetylated 2-azido-2-deoxy glycosyl nitrates. These nitrates can be used to prepare 2-amino-2-deoxy sugars, such as D-galactosamine and lactosamine. The O-acetylated 2-azido-2-deoxy glycosyl nitrates can alternately be converted to O-acetylated 2-azido-2-deoxy glycosyl halides which are useful in the preparation of O-acetylated 2-azido-2-deoxy glycosides, which in turn can be reduced to 2-amino-2-deoxy glycosides. Of particular interest are the syntheses of 2-amino-2-deoxy glycosides which correspond to the terminal units of the antigenic determinant for the human A blood group. Attachment of these glycosides to a solid support provides immunoabsorbents which efficiently and preferentially absorb anti-A antibodies from blood plasma.
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