- A silyl ether-protected building block forO-GlcNAcylated peptide synthesis to enable one-pot acidic deprotection
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In this report, we introduce a novel building block for Fmoc/tBu solid phase peptide synthesis (SPPS) of β-linkedO-GlcNAcylated peptides. This building block carries acid labile silyl ether protecting groups, which are fully removed under TFA-mediated peptide cleavage conditions from the resin, thus requiring fewer synthetic steps and no intermediate purification as compared to other acid or base labile protecting group strategies.
- Yan, Bingjia,Li, Wenyi,Hackenberger, Christian P. R.
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supporting information
p. 8014 - 8017
(2021/10/04)
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- Enhanced epimerization of glycosylated amino acids during solid-phase peptide synthesis
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Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the α position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens. This article not subject to U.S. Copyright. Published 2012 by the American Chemical Society.
- Zhang, Yalong,Muthana, Saddam M.,Farnsworth, David,Ludek, Olaf,Adams, Kristie,Barchi, Joseph J.,Gildersleeve, Jeffrey C.
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supporting information; experimental part
p. 6316 - 6325
(2012/05/07)
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- O-GlcNAc peptide epoxyketones are recognized by mammalian proteasomes
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(Chemical Equation Presented) Cytosolic and nuclear proteins may be subject to both O-GlcNAcylation and proteasomal degradation. By means of activity-based profiling, we demonstrate that O-GlcNAc serinecontaining peptide epoxyketones bind to the proteasome catalytic active sites and thus provide the first clear evidence that proteasomes recognize peptides post-translationally modified with a GlcNAc moiety.
- Witte, Martin D.,Florea, Bogdan I.,Verdoes, Martijn,Adeyanju, Oloruntosin,Van Der Marel, Gijs A.,Overkleeft, Herman S.
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supporting information; experimental part
p. 12064 - 12065
(2010/01/30)
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