Site Specific Preparation of <i>N‐</i>Glycosylated Peptides: Thioamide‐Directed Activation of Aspartate

Taresh, Ameer Badri; Hutton, Craig A.

doi:10.1002/anie.202210367

Cited by 8 publications

(4 citation statements)

References 38 publications

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“…Another interesting discovery for the convergent synthesis of N‐linked glycopeptides is the thioamide‐directed activation of aspartate strategy (Figure 1, Approach C). [ 29 ] Basically, the incorporation of a thioamide N‐terminal to an Asp residue facilitates Ag(I)‐promoted conversion into respective N ‐ glycosylated Asn residue in the presence of a glycosyl amine. An optimal result was obtained when using 1.2 equiv.…”

Section: Methods Development Towards Efficient Assembly Of Glycoproteinsmentioning

confidence: 99%

Recent Advances in Glycopeptide and Glycoprotein Synthesis: A Refined Synthetic Probe towards the Biological World

et al. 2023

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Comprehensive Summary Protein glycosylation is the most complex and diverse form of post‐translational modification in human body. Meanwhile, glycosylation of peptides and proteins emerges as a promising strategy to improve the pharmacokinetic profile of peptide‐ and protein‐based therapeutics. Owing to the importance of protein glycosylation, a rigorous evaluation of the relationship between the precise structure and biological function of glycoproteins has to be performed. Recently, chemical synthesis, chemoenzymatic synthesis and semisynthesis strategies have attracted extensive attentions towards the preparation of structurally defined glycopeptides and glycoproteins; the obtained synthetic glycoforms thus enable the thorough investigation of specific effects of protein glycosylation. This review highlights the recent progress in the development of novel strategies, preparation of homogeneous glycoproteins and exploration of structure‐activity relationships. On this basis, the challenges and prospects are discussed.

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Section: Methods Development Towards Efficient Assembly Of Glycoproteinsmentioning

confidence: 99%

Recent Advances in Glycopeptide and Glycoprotein Synthesis: A Refined Synthetic Probe towards the Biological World

et al. 2023

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“…[108] Most recently, the group has further developed the method to achieve late stage glycosylation, by converting aspartate residues to N-glycosylated asparagine residues (Scheme 16C). [109] Ibara et al have similarly used Ag(I) to selectively replace carbamates at the N-terminus of thiopeptides (Scheme 16D). [110] Thus, achieving the substitution of the tert-butyl alcohol in the Boc group with benzyl alcohol to convert a Boc group to a Cbz group.…”

Section: Synthetic Applications Of Thioamidesmentioning

confidence: 99%

“…Furthermore, the method has been utilized for lactam stapling [107] and macrolactonization [108] . Most recently, the group has further developed the method to achieve late stage glycosylation, by converting aspartate residues to N ‐glycosylated asparagine residues (Scheme 16C) [109] …”

Section: Applications Of Thioamidesmentioning

confidence: 99%

Contemporary Applications of Thioamides and Methods for Their Synthesis

Hansen,

Olsen

2023

Chemistry A European J

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Thioamides are naturally occurring isosteres of amide bonds in which the chalcogen atom of the carbonyl is changed from oxygen to sulfur. This substitution gives rise to altered nucleophilicity and hydrogen bonding properties with importance for both chemical reactivity and non‐covalent interactions. As such, thioamides have been introduced into biologically active compounds to achieve improved target affinity and/or stability towards hydrolytic enzymes but have also been applied as probes of protein and peptide folding and dynamics. Recently, a series of new methods have been developed for the synthesis of thioamides as well as their utilization in peptide chemistry. Further, novel strategies for the incorporation of thioamides into proteins have been developed, enabling both structural and functional studies to be performed. In this Review, we highlight the recent developments in the preparation of thioamides and their applications for peptide modification and study of protein function.

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“…In post-assembly glycosylation, glycosylation takes place after the peptide is synthesized. Several post-assembly glycosylation methods have been developed over the years, 8 typically via Lansbury aspartylation in which an aminosugar reacts with the activated aspartic acid side-chain to form the N-glycan. [9][10][11] The main shortcoming of this method was the formation of several prominent side reactions such as cyclic aspartimide.…”

Section: Introductionmentioning

confidence: 99%

Accelerated solid-phase synthesis of glycopeptides containing multipleN-glycosylated sites

et al. 2023

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Site Specific Preparation of N‐Glycosylated Peptides: Thioamide‐Directed Activation of Aspartate

Abstract: A site-specific method for the preparation of N-glycosylated peptides is described. Incorporation of a peptide backbone thioamide linkage adjacent to an Asp residue facilitates a Ag I -promoted, site-specific conversion to N-glycosylated Asn residues in peptides.

Cited by 8 publications

References 38 publications

Recent Advances in Glycopeptide and Glycoprotein Synthesis: A Refined Synthetic Probe towards the Biological World

Recent Advances in Glycopeptide and Glycoprotein Synthesis: A Refined Synthetic Probe towards the Biological World

Contemporary Applications of Thioamides and Methods for Their Synthesis

Accelerated solid-phase synthesis of glycopeptides containing multipleN-glycosylated sites

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