- Syntheses of TN building blocks Nα-(9- fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D- galactopyranosyl)-L-serine/L-threonine pentafluorophenyl esters: Comparison of protocols and elucidation of side reactions
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TN antigen building blocks Nα-(9- fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-d- galactopyranosyl)-l-serine/l-threonine pentafluorophenyl ester [Fmoc-l-Ser/l-Thr(Ac3-α-d-GalN3)-OPfp, 13/14]
- Liu, Mian,Young Jr., Victor G.,Lohani, Sachin,Live, David,Barany, George
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- Positional Scanning MUC1 Glycopeptide Library Reveals the Importance of PDTR Epitope Glycosylation for Lectin Binding
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One of the main barriers to explaining the functional significance of glycan-based changes in cancer is the natural epitope heterogeneity found on the surface of cancer cells. To help address this knowledge gap, we focused on designing synthetic tools to explore the role of tumor-associated glycans of MUC1 in the formation of metastasis via association with lectins. In this study, we have synthesized for the first time a MUC1-derived positional scanning synthetic glycopeptide combinatorial library (PS-SGCL) that vary in number and location of cancer-associated Tn antigen using the "tea bag" approach. The determination of the isokinetic ratios necessary for the equimolar incorporation of (glyco)amino acids mixtures to resin-bound amino acid was determined, along with developing an efficient protocol for on resin deprotection of O-acetyl groups. Enzyme-linked lectin assay was used to screen PS-SGCL against two plant lectins, Glycine max soybean agglutinin and Vicia villosa. The results revealed a carbohydrate density-dependent affinity trend and site-specific glycosylation requirements for high affinity binding to these lectins. Hence, PS-SGCLs provide a platform to systematically elucidate MUC1-lectin binding specificities, which in the long term may provide a rational design for novel inhibitors of MUC1-lectin interactions involved in tumor spread and glycopeptide-based cancer vaccines.
- Singh, Yashonandini,Rodriguez Benavente, Maria C.,Al-Huniti, Mohammed H.,Beckwith, Donella,Ayyalasomayajula, Ramya,Patino, Eric,Miranda, William S.,Wade, Alex,Cudic, Maré
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p. 1434 - 1445
(2020/01/02)
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- Synthesis of major histocompatibility complex class I binding glycopeptides
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Four Major Histocompatibility Complex (MHC) Class I binding glycopeptides and two peptide analogues, from a cytotoxic T-lymphocyte (CTL) epitope of Sendai Virus Nucleoprotein, have been prepared using solid-phase peptide synthesis employing the following glycosyl amino acid building blocks: FmocSer(Ac3-β-D-GlcNAc)OH 1, FmocSer(Ac3-α-D-GalN3)OPfp 2, FmocAsn(Ac3-β-D-GlcNAc)OH 3 and FmocAsn(ac3-β-D-GalNAc)OH 4.Previously, we examined the influence of glycosylation on peptide binding to the MHC Class I molecule and CTL recognition of these peptides.The synthesis and characterization of compounds 1-4 as well as the resulting glycopeptides is described.In addition, results of NMR investigations demonstrating that peptide K3, and glycopeptides K3-O-GlcNAc and K3-O-GalNAc, show two distinct conformations in solution as a result of cis-trans isomerization about a Tyr-Pro amide bond are reported.
- Arsequell, Gemma,Haurum, John S.,Elliott, Tim,Dwek, Raymond A.,Lellouch, Annemarie C.
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p. 1739 - 1746
(2007/10/02)
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- A New Strategy for the Solid-Phase Synthesis of O-Glycopeptides via 2-Azido-glycopeptides
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The building blocks Fmoc-Thr(α-D-GalN3Ac3)-OPfp (8) and Fmoc-Ser(α-D-GalN3Ac3)-OPfp (9) were synthesized.Both building blocks are active esters which can directly be used for the solid-phase synthesis of O-glycopeptides.The obtained glycopeptides carry an
- Paulsen, Hans,Bielfeldt, Tim,Peters, Stefan,Meldal, Morten,Bock, Klaus
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p. 369 - 380
(2007/10/02)
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