Synthesis of C-Glycosyl Amino Acid Building Blocks Suitable for the Solid-Phase Synthesis of Multivalent Glycopeptide Mimics

Five C-glycosyl functionalized lysine building blocks, featuring C-glycosidic derivatives of alpha-rhamnose, alpha-mannose, alpha-galactose, beta-galactose, and beta-N-acetyl glucosamine have been designed and synthesized. These derivatives, equipped with acid-labile protecting groups, are eminently suitable for solid-phase synthesis of multivalent glycopeptides. The lysine building blocks were prepared fromC-allyl glycosides that underwent a Grubbs cross-metathesis with an acrylate, followed by a reduction of the C=C double bond in the resulting alpha,beta-unsaturated esters, and liberation of the carboxylate to allow condensation with a lysine side chain. The thus obtainedC-glycosides, five in total, were applied in the solid-phase peptide synthesis (SPPS) of three glycopeptides, showing the potential of the described building blocks in the assembly of well-defined mimics of homo- and heteromultivalent glycopeptides and glycoclusters.Bio-organic Synthesi

ssPNA templated assembly of oligo(p-phenylenevinylene)s

peer reviewe

Monitoring Alzheimer Amyloid Peptide Aggregation by EPR

Plaques containing the aggregated β-Amyloid (Aβ) peptide in the brain are the main indicators of Alzheimer’s disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of Aβ. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue Aβ peptide variant containing an N-terminal cysteine (cys-Aβ) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Δ-pyrroline-3-methyl] methanethiosulfonate spin label (SL-Aβ). Fibril formation in solutions of pure SL-Aβ and of SL-Aβ mixed with Aβ was shown by Congo-red binding and electron microscopy. Continuous-wave 9 GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric Aβ, one to a multimer (8–15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation

Synthesis and evaluation of fluorescent Pam(3)Cys peptide conjugates

Tumorimmunolog

Design, automated synthesis and immunological evaluation of NOD2-ligand-antigen conjugates

Tumorimmunolog

Conjugation of nucleosides and oligonucleotides by [3+2] cycloaddition

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Synthesis of Sugar Nucleotides by Application of Phosphoramidites

new method for the construction of pyrophosphates is reported based on the coupling of a sugar phosphate and a nucleoside phosphoramidite. The in situ formed phosphate¿phosphite intermediate was subsequently oxidized with tBuOOH. Three UDP-N-acetylglucosamine derivatives were prepared using this one-pot procedure in good yields

Amyloid-like behavior of site-specifically citrullinated myelin oligodendrocyte protein (MOG) peptide fragments inside EBV infected B-cells influences their cytotoxicity and autoimmunogenicity

Multiple Sclerosis (MS) is an autoimmune disorder manifested via chronic inflammation, demyelination and neurodegeneration inside the central nervous system (CNS). The progressive phase of MS is characterized by neurodegeneration, but unlike classical neurodegenerative diseases, amyloid-like aggregation of self-proteins has not been documented. There is evidence that citrullination protects an immunodominant peptide of human myelin oligodendrocyte glycoprotein (MOG34-56) against destructive processing in EBV-infected B-lymphocytes (EBV-BLCs) in marmosets and causes exacerbation of ongoing MS-like encephalopathies in mice. Here we collected evidence that citrullination of MOG can also lead to amyloid-like behavior shifting the disease pathogenesis towards neurodegeneration. We observed that an immunodominant MOG peptide, MOG35-55, displays amyloid-like behavior upon site-specific citrullination at positions 41, 46 and/or 52. These amyloid aggregates are shown to be toxic to the EBV-BLCs, and to dendritic cells, at concentrations favored for antigen presentation suggesting a role of amyloid-like aggregation in the pathogenesis of progressive MS.Bio-organic Synthesi

Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism

Host-parasite interactio