- Piperidine is preferred to morpholine for Fmoc cleavage in solid phase glycopeptide synthesis as exemplified by preparation of glycopeptides related to HIV gp120 and mucins
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Protected derivatives of the Tn antigens [Fmoc-Ser/Thr(Ac3GalNAcα)-OH, compounds 5 and 8] have been prepared by glycosylation of Fmoc-Ser/Thr- OAllyl with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-D-galactopyranosyl chloride (2), followed by conversion of the azido group to an acetamide and deallylation. The derivatives 5 and 8 were used for solid phase synthesis of glycopeptides related to HIV gp120 and mucins. In these syntheses piperidine was found to give efficient Fmoc removal whereas deprotection with morpholine was slow and incomplete for some steps. In contrast to previous concerns β- elimination and epimerization of glycopeptide stereocenters was not encountered when piperidine was used for Fmoc deprotection. However, it was found that for glycopeptides which contained cysteine residues, de-O- acetylation with methanolic ammonia had to be performed before side-chain deprotection and cleavage from the solid phase.
- Vuljanic, Tatjana,Bergquist, Karl-Erik,Clausen, Henrik,Roy, Sarbani,Kihlberg, Jan
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- Antifreeze glycopeptide analogues: Microwave-enhanced synthesis and functional studies
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Antifreeze glycoproteins enable life at temperatures below the freezing point of physiological solutions. They usually consist of the repetitive tripeptide unit (-Ala-Ala-Thr-) with the disaccharide α-d-galactosyl-(1-3) -β-N-acetyl-d-galactosamine attached to each hydroxyl group of threonine. Monoglycosylated analogues have been synthesized from the corresponding monoglycosylated threonine building block by microwave-assisted solid phase peptide synthesis. This method allows the preparation of analogues containing sequence variations which are not accessible by other synthetic methods. As antifreeze glycoproteins consist of numerous isoforms they are difficult to obtain in pure form from natural sources. The synthetic peptides have been structurally analyzed by CD and NMR spectroscopy in proton exchange experiments revealing a structure as flexible as reported for the native peptides. Microphysical recrystallization tests show an ice structuring influence and ice growth inhibition depending on the concentration, chain length and sequence of the peptides.
- Heggemann, Carolin,Budke, Carsten,Schomburg, Benjamin,Majer, Zsuzsa,Wibrock, Marco,Koop, Thomas,Sewald, Norbert
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- Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)
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Antifreeze glycoproteins are a class of biological agents which enable living at temperatures below the freezing point of the body fluids. Antifreeze glycopeptides usually consist of repeating tripeptide unit (-Ala-Ala-Thr?-), glycosylated at the threonine side chain. However, on the microscopic level, the mechanism of action of these compounds remains unclear. As previous research has shown, antifreeze activity of antifreeze glycopeptides strongly relies on the overall conformation of the molecule as well an on the stereochemistry of amino acid residues. The desired monoglycosylated analogues with acetylated amino termini and the carboxy termini in form of N-methylamide have been synthesized. Conformational nuclear magnetic resonance (NMR) studies of the designed analogues have shown a strong influence of the stereochemistry of amino acid residues on the peptide chain stability, which could be connected to the antifreeze activity of these compounds. A better understanding of the mechanism of action of antifreeze glycopeptides would allow applying these materials, e.g., in food industry and biomedicine.
- Urbańczyk, Ma?gorzata,Jewgiński, Micha?,Krzciuk-Gula, Joanna,Góra, Jerzy,Latajka, Rafa?,Sewald, Norbert
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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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- Methyl esters: an alternative protecting group for the synthesis of O-glycosyl amino acid building blocks
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The glycosyl amino acids α-GalNAc-Ser and α-GalNAc-Thr are fundamental building blocks for glycopeptide synthesis, Schmidt's synthesis method often being chosen for this purpose. Methyl esters used as orthogonal carboxylic acid protecting group in this pr
- Mayato, Carlos,Dorta, Rosa L.,Vázquez, Jesús T.
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- Chemoenzymatic synthesis of glycosylphosphatidylinositol-anchored glycopeptides
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MUC1 glycopeptide was efficiently coupled to glycosylphosphatidylinositol (GPI) derivatives by sortase A (SrtA), verifying that SrtA can accept sterically hindered glycopeptide as substrate for ligation with GPIs. This work has established a practical method for the chemoenzymatic synthesis of GPI-linked glycopeptides.
- Wu, Zhimeng,Guo, Xueqing,Guo, Zhongwu
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- Fluorenylmethoxycarbonyl-Protected O-Glycosyl-N-methyl Amino Acids: Building Blocks for the Synthesis of Conformationally Tuned Glycopeptide Antigens
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Peptide antibiotics often contain N-methylated amino acids. These N-methylamino components enhance the metabolic stability and strongly influence the conformational behavior of these peptide drugs. N-Methyl-O-glycosyl amino acids, in particular, threonine and serine derivatives, are unknown so far. Fmoc-protected N-methyl-O-glycosyl-threonine and -serine building blocks, including sialyl TN antigens, have been synthesized for the first time by converting the Fmoc-protected O-glycosyl amino acids or their tert-butyl esters into the corresponding oxazolidinones followed by reductive ring-opening. These new components are considered interesting for the construction of modified mucin glycopeptide anti-tumor vaccines with extended biological half-life. Fmoc-protected building blocks of N-methylated O-glycosyl amino acids, inaccessible so far, have been synthesized by the conversion of Fmoc-O-glycosyl amino acids into the corresponding oxazolidines followed by reductive ring-opening. These N-methyl-O-glycosyl amino acids could be used in solid-phase glycopeptide syntheses under particular conditions.
- Buba, Annette E.,L?we, Holger,Kunz, Horst
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- Revealing Functional Significance of Interleukin-2 Glycoproteoforms Enabled by Expressed Serine Ligation
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Naturally occurring interleukin-2 (IL-2) is a pleiotropic glycoprotein that regulates immune responses by controlling the differentiation and homeostasis of T cells. Non-glycosylated IL-2 has been used in clinical settings for three decades. However, the function of the O-glycan of native IL-2 remains elusive. Herein, to stress this issue, we report a highly efficient semi-synthesis of homogeneous glycosylated IL-2 with various glycoproteoforms on a multi-milligram scale. The glycopeptide fragment was prepared by chemical synthesis and then merged with recombinant fragment via a serine ligation to generate the desired glycoprotein in a single operation. Biological evaluation of the homogenous glycoprotein library reveals that the activity of IL-2 in activating individual T cell subset is glycan dependent, thus highlighting the possibility of further improving current clinical medicine.
- Cao, Qi,Li, Bin,Liu, Jiazhi,Liu, Lizhen,Liu, Xinnan,Shao, Hong,Tao, Houchao,Wang, Can,Wang, Ping,Xue, Dongxiang,Ye, Farong,Yu, Biao,Zhao, Hongbo,Zhao, Jie
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supporting information
(2022/01/31)
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- Design and synthesis of trivalent Tn glycoconjugate polymers by nitroxide-mediated polymerization
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A new synthetic method for preparing Tn glycoconjugate polymers, containing tumor-associated carbohydrate antigens, by controlled living radical polymerization is reported. To mimic the authentic structures of Tn glycopeptide antigens and to explore the controlled living radical polymerization, three tumor-associated carbohydrate antigens (GalNAc, GalNAcα1-O-Ser, and GalNAcα1-O-Thr) were attached to a styrene-type monomer through a diethylene glycol spacer. Under nitroxide-mediated polymerization, controlled living radical polymerization proceeded to afford defined glycopeptide polymers with different Tn densities and compositions. The polydispersity index (PDI) and molecular weights were increased and conversions were decreased upon increasing the concentration of Tn glycoconjugate monomers. The resulting Tn glycoconjugate polymers were characterized by NMR and IR. The spectral data indicate that the Tn glycoconjugate moiety did attach to the polymer chain and Tn glycoconjugate density could be adjusted through the nitroxide-mediated polymerization conditions. The number of Tn units containing in the polymer chains could be estimated by NMR integration. This synthetic approach provides a new and efficient tool for constructing novel Tn glycoconjugate polymers.
- Liu, Si-Xian,Tsai, Yun-Tzu,Lin, Yu-Tung,Li, Jia-Yue,Chang, Che-Chien
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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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- Synthetic MUC1 antitumor vaccine with incorporated 2,3-sialyl-T carbohydrate antigen inducing strong immune responses with isotype specificity
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The endothelial glycoprotein MUC1 is known to underlie alterations in cancer by means of aberrant glycosylation accompanied by changes in morphology. The heavily shortened glycans induce a collapse of the peptide backbone and enable accessibility of the latter to immune cells, rendering it a tumor-associated antigen. Synthetic vaccines based on MUC1 tandem repeat motifs, comprising tumor-associated 2,3-sialyl-T antigen, conjugated to the immunostimulating tetanus toxoid, are reported herein. Immunization with these vaccines in a simple water/oil emulsion produced a strong immune response in mice to which stimulation with complete Freund’s adjuvant (CFA) was not superior. In both cases, high levels of IgG1 and IgG2a/b were induced in C57BL/6 mice. Additional glycosylation in the immunodominant PDTRP domain led to improved binding of the induced antisera to MCF-7 breast tumor cells, compared with that of the monoglycosylated peptide vaccine.
- Stra?burger, David,Glaffig, Markus,Stergiou, Natascha,Bialas, Sabrina,Besenius, Pol,Schmitt, Edgar,Kunz, Horst
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p. 1142 - 1146
(2018/10/21)
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- A Synthetic MUC1 Glycopeptide Bearing βGalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells
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This study presents the synthesis of the novel protected O-glycosylated amino acid derivatives 1 and 2, containing βGalNAc-SerOBn and βGalNAc-ThrOBn units, respectively, as mimetics of the natural Tn antigen (αGalNAc-Ser/Thr), along with the solid-phase assembly of the glycopeptides NHAcSer-Ala-Pro-Asp-Thr[αGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (3-BSA) and NHAcSer-Ala-Pro-Asp-Thr[βGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (4-BSA), bearing αGalNAc-Thr or βGalNAc-Thr units, respectively, as mimetics of MUC1 tumor mucin glycoproteins. According to ELISA tests, immunizations of mice with βGalNAc-glycopeptide 4-BSA induced higher sera titers (1:320 000) than immunizations with αGalNAc-glycopeptide 3-BSA (1:40 000). Likewise, flow cytometry assays showed higher capacity of the obtained anti-glycopeptide 4-BSA antibodies to recognize MCF-7 tumor cells. Cross-recognition between immunopurified anti-βGalNAc antibodies and αGalNAc-glycopeptide and vice versa was also verified. Lastly, molecular dynamics simulations and surface plasmon resonance (SPR) showed that βGalNAc-glycopeptide 4 can interact with a model antitumor monoclonal antibody (SM3). Taken together, these data highlight the improved immunogenicity of the unnatural glycopeptide 4-BSA, bearing βGalNAc-Thr as Tn antigen isomer.
- Leiria Campo, Vanessa,Riul, Thalita B.,Oliveira Bortot, Leandro,Martins-Teixeira, Maristela B.,Fiori Marchiori, Marcelo,Iaccarino, Emanuela,Ruvo, Menotti,Dias-Baruffi, Marcelo,Carvalho, Ivone
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p. 527 - 538
(2017/03/22)
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- Synthesis of tumor-associated MUC1-glycopeptides and their multivalent presentation by functionalized gold colloids
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The mucin MUC1 is a glycoprotein involved in fundamental biological processes, which can be found over-expressed and with a distinctly altered glycan pattern on epithelial tumor cells; thus it is a promising target structure in the quest for effective carbohydrate-based cancer vaccines and immunotherapeutics. Natural glycopeptide antigens indicate only a low immunogenicity and a T-cell independent immune response; however, this major drawback can be overcome by coupling of glycopeptide antigens multivalently to immunostimulating carrier platforms. In particular, gold nanoparticles are well suited as templates for the multivalent presentation of glycopeptide antigens, due to their remarkably high surface-to-volume ratio in combination with their high biostability. In this work the synthesis of novel MUC1-glycopeptide antigens and their coupling to gold nanoparticles of different sizes are presented. In addition, the development of a new dot-blot immunoassay to test the potential antigen-antibody binding is introduced.
- Tavernaro, Isabella,Hartmann, Sebastian,Sommer, Laura,Hausmann, Heike,Rohner, Christian,Ruehl, Martin,Hoffmann-Roeder, Anja,Schlecht, Sabine
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- Scalable synthesis of Fmoc-protected GalNAc-threonine amino acid and TN antigen via nickel catalysis
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The highly α-selective and scalable synthesis of the Fmoc-protected GalNAc-threonine amino acid and TN antigen in gram scale (0.5-1 g) is described. The challenging 1,2-cis-2-amino glycosidic bond is addressed through a coupling of threonine residues with C(2)-N-ortho-(trifluoromethyl)benzylidenamino trihaloacetimidate donors mediated by Ni(4-F-PhCN)4(OTf)2. The desired 1,2-cis-2-amino glycoside was obtained in 66% yield (3.77 g) with α-only selectivity and subsequently transformed into the Fmoc-protected GalNAc-threonine and TN antigen. This operationally simple procedure no longer requires utilization of the commonly used C(2)-azido donors and overcomes many of the limitations associated with the synthesis of 1,2-cis linkage.
- Yu, Fei,McConnell, Matthew S.,Nguyen, Hien M.
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p. 2018 - 2021
(2015/04/27)
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- Glycosylated analogs of formaecin I and drosocin exhibit differential pattern of antibacterial activity
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The synthetic glycopeptides are interesting model systems to study the effect of O-glycosylation in modulating their function and structure. A series of glycosylated analogs of two antibacterial peptides, formaecin I and drosocin, were synthesized by varying the nature of sugar and its linkage with bioactive peptides to understand the influence of structure variation of glycosylation on their antibacterial activities. Higher antibacterial activities of all glycopeptides compared to their respective non-glycosylated counterparts emphasize in part the importance of sugar moieties in functional implications of these peptides. The consequences of the unique differences among the analogs were apparent on their antibacterial activities but not evident structurally by circular dichroism studies. We have shown that differently glycosylated peptides exhibit differential effect among each other when tested against several Gram-negative bacterial strains. The change of monosaccharide moiety and/or its anomeric configuration in formaecin I and drosocin resulted into decrease in the antibacterial activity in comparison to that of the native glycopeptide, but the extent of decrease in antibacterial activity of glycosylated drosocin analogs was less. Probably, the variation in peptide conformation arising due to topological dissimilarities among different sugars in the same peptide resulting in possible modulation in binding properties appears to be responsible for differences in their antibacterial activities. Indeed, these effects of glycosylation are found to be sequence-specific and depend in the milieu of amino acid residues. Interestingly, none of the carbohydrate variants affected the basic property of these peptides, which is non-hemolytic and non-toxicity to eukaryotic cells. The Author(s) 2011.
- Talat, Sariya,Thiruvikraman, Menithalakshmi,Kumari, Saroj,Kaur, Kanwal J.
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p. 537 - 555
(2014/02/14)
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- Functional and structural characterization of drosocin and its derivatives linked O-GalNAc at Thr11 residue
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Antimicrobial peptides have recently gained the much attention because of their ability to make defense system from attacking bacterial infections. Drosocin has been considered as very attractive antibiotic agents because of low toxicity against human erythrocytes and active at the low concentration. We have studied the structureactivity relationship of a glycopeptide drosocin focused on the N-acetyl-D-galactoside at Thr11 residue. Based on the radial diffusion assay, we found that the acetylation of carbohydrate moiety increased the antimicrobial activity and the Pro10, present in the middle of drosocin plays an important role in the antimicrobial activity. Our results provide a good lead compound for further studies on the design of drosocin-based analogues targeting glyco linked Thr site.
- Ahn, Mija,Sohn, Hoik,Nan, Yong Hai,Murugan, Ravichandran N.,Cheong, Chaejoon,Ryu, Eun Kyoung,Kim, Eun-Hee,Kang, Shin Won,Kim, Eun Joo,Shin, Song Yub,Bang, Jeong Kyu
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experimental part
p. 3327 - 3332
(2012/02/04)
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- Synthesis of Tn/T antigen MUC1 glycopeptide BSA conjugates and their evaluation as vaccines
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The tumor-associated mucin MUC1 over-expressed in most epithelial tumor tissues is considered a promising target for immunotherapy. The extracellular part of MUC1 contains a domain of numerous tandem repeats of the amino acid sequence HGVTSAPDTRPAPGSTAPPA, including five potential O-glycosylation sites. In this study, T9 and S15 have been chosen as the positions of glycosylation. The glycopeptides N-terminally equipped with a triethylene glycol spacer were synthesized by microwave-assisted Fmoc solid-phase peptide synthesis. After detachment from the resin and deprotection, the MUC1 glycopeptides were conjugated to bovine serum albumin (BSA). To evaluate the immunological properties, balb/c mice were immunized with these BSA vaccines. Copyright
- Cai, Hui,Huang, Zhi-Hua,Shi, Lei,Zou, Peng,Zhao, Yu-Fen,Kunz, Horst,Li, Yan-Mei
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scheme or table
p. 3685 - 3689
(2011/09/21)
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- Extended sugar-assisted glycopeptide ligations: Development, scope, and Applications
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Recently, we reported the development of sugar-assisted ligation (SAL), a novel peptide ligation method for the synthesis of glycopeptides. After screening a large number of glycoprotein sequences in a glycoprotein database, it became evident that a large proportion (approximately 53%) of O-glycosylation sites contain amino acid residues that will not undergo SAL reactions. To overcome these inherent limitations and broaden the scope of the method we report here the development of an extended SAL method. Glycopeptides containing up to six amino acid extensions N-terminal to the glycosylated residue were shown to facilitate ligation reactions with peptide thioesters, and these products were isolated in good yields. Kinetic analysis was used to show that as glycopeptides were extended by further amino acid residues, ligation reactions became slower. This finding was rationalized by molecular dynamics simulations using AMBER9. These studies suggested a general trend whereby the proximal distance between the reactive sites of the thioester intermediate (the N-terminal amine and the carbonyl carbon of the thioester) increased as glycopeptides were extended, thus slowing down the ligation rate. Each of the extended SAL methods showed broad tolerance to a number of different amino acid combinations at the ligation junction. Re-evaluation of the glycoprotein database suggested that 95% of the O-linked glycosylation sites can now be utilized to facilitate SAL or extended SAL reactions. As such, this method represents an extremely valuable tool for the synthesis of naturally occurring glycopeptides and glycoproteins. To demonstrate the applicability of the method, extended SAL was successfully implemented in the synthesis of the starting unit of the cancer-associated MUC1 glycoprotein.
- Payne, Richard J.,Ficht, Simon,Tang, Sishi,Brik, Ashraf,Yang, Yu-Ying,Case, David A.,Wong, Chi-Huey
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p. 13527 - 13536
(2008/09/17)
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- Site-specific incorporation of the mucin-type N-acetylgalactosamine- α-O-threonine into protein in Escherichia coli
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Glycosylation is a prevalent posttranslational process capable of augmenting and modulating protein function. Efficient synthesis of high-purity, homogeneous glycoproteins is essential for the study of unique protein glycoforms and for the manufacture of therapeutically relevant forms. A promising new strategy for controlled in vivo synthesis of glycoproteins was recently established using suppressor tRNA technology. Using an evolved tRNA aminoacyl synthetase-tRNA pair from Methanococcus jannaschii, the glycosyl amino acid, N-acetylglucosamine-β-O-serine (GlcNAc-β-Ser), was site-specifically introduced into proteins cotranslationally in Escherichia coli. Herein, we report the evolution of a new tRNA aminoacyl synthetase-tRNA pair that has expanded the repertoire of glycoproteins that can be expressed in E. coli to contain the other major O-linked glycan, N-acetylgalactosamine-α-O-threonine (GalNAc-a-Thr). Copyright
- Xu, Ran,Hanson, Sarah R.,Zhang, Zhiwen,Yang, Yu-Ying,Schultz, Peter G.,Wong, Chi-Huey
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p. 15654 - 15655
(2007/10/03)
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- Synthetic Glycopeptides of the Tandem Repeat Sequence of the Epithelial Mucin MUC4 with Tumour-associated Carbohydrate Antigens
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Glycohexadecapeptides representing the tandem repeat sequence of the epithelial mucin MUC4 were prepared by applying a solid-phase methodology. The required glycosyl amino acid building blocks containing the tumour-associated saccharide antigens TN/
- Brocke, Constanze,Kunz, Horst
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p. 2052 - 2056
(2007/10/03)
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- Nitroglycal concatenation: A broadly applicable and efficient approach to the synthesis of complex O-glycans
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Base-catalyzed glycosylations provide the basis for a new and general entry to the synthesis of mucin-type O-glycans. The desired α-linked 2-acetamidoglycosyl amino acids B are accessible selectively starting from glycals of type A. Fmoc = 9-fluorenylmeth
- Winterfeld, Gottfried A.,Schmidt, Richard R.
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p. 2654 - 2657
(2007/10/03)
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- A novel and efficient route towards α-GalNAc-Ser and α-GalNAc-Thr building blocks for glycopeptide synthesis
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Michael addition of serine and threonine derivatives 4a-4c to 3,4,6-tri- O-benzyl-2-nitro-D-galactal (1) afforded the corresponding 2-deoxy-2-nitro- α-D-galactopyranosides 5a-5c in good yield and stereoselectivity. 2-deoxy-2- nitroglycosides 5a and 5b were reduced to the 2-acetamido compounds by platinized Raney nickel T4. Manipulation of the protecting groups afforded known N-Fmoc-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D- galactopyranosyl)-L-serine (8a) and -threonine (8b), valuable building blocks for O-glycopeptide synthesis.
- Winterfeld, Gottfried A.,Ito, Yukishige,Ogawa, Tomoya,Schmidt, Richard R.
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p. 1167 - 1171
(2007/10/03)
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- Synthetic and immunological studies on clustered modes of mucin-related Tn and TF O-linked antigens: The preparation of a glycopeptide-based vaccine for clinical trials against prostate cancer
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The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved using glycal assembly and cassette methodologies. These synthetic antigens were subsequently clustered (c) and immunoconjugated to a carrier protein (KLH or BSA) or
- Kuduk, Scott D.,Schwarz, Jacob B.,Chen, Xiao-Tao,Glunz, Peter W.,Sames, Dalibor,Ragupathi, Govindaswami,Livingston, Philip O.,Danishefsky, Samuel J.
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p. 12474 - 12485
(2007/10/03)
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- Stereoselective synthesis of O-serinyl/threoninyl-2-acetamido-2-deoxy-α- or β-glycosides
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General glycosidation methodology has been developed which can selectively provide 2-acetamido-2-deoxy-α- or β-glycosides of β-hydroxy-α-amino acid derivatives [glucopyranoside-(8, 43), galactopyranoside- (9, 13), mannopyranoside- (10), lactoside analogs (11, 38) and 3-O-β-galactopyranosyl-mannopyranoside (12)] stereoselectively in excellent yield from the highly nucleophilic α-imino esters (Schiff bases) of L-serine and L-threonine. Various glycosides were converted via their amino and acetamido derivatives to Fmoc-protected serinyl- or threoninyl-glycosides (24-28, 37, 41, 46) which are all suitable building blocks for the solid-phase synthesis of O-glycopeptides. Complete 1H- and 13C-NMR data are provided for all compounds.
- Szabo,Ramza,Langdon,Polt
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- Synthesis of O-Glycopeptides of the N-Terminus of Interleukin-2
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The synthesis of a number of O-glycopeptides with different lengths of chain of between 3 and 10 amino acids that are part of the N-terminus of interleukin-2 is described.The key intermediate for the syntheses is O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-galactopyranosyl)-N-(9-fluorenylmethoxycarbonyl)-L-threonine tert-butyl ester (9b), to which suitably protected amino acids and peptides can be added C- or N-terminally. 9b is an element, which allows to insert glycosylated hydroxyamino acids with the Fmoc/tBu combination of protective groups, which are approved in peptide synthesis.During the syntheses peptide blocks are used.With the deprotected products it is possible to test the structural specificity of glycosyl transferases.
- Paulsen, Hans,Adermann, Knut
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p. 751 - 770
(2007/10/02)
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- Synthesis of Varied O-Glycopeptides of Interleukin-2
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A number of O-glycopeptides, which are varieties of the N-terminus of interleukin-2, is synthesized.In these compounds a modified amino acid sequence, an altered glycosylation site, or a higher level of glycosylation is achieved.The syntheses are carried
- Paulsen, Hans,Adermann, Knut
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p. 771 - 780
(2007/10/02)
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