Prevention of aspartimide formation during peptide synthesis using cyanosulfurylides as carboxylic acid-protecting groups

Open access
Date
2020Type
- Journal Article
Citations
Cited 14 times in
Web of Science
Cited 16 times in
Scopus
ETH Bibliography
yes
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Abstract
Although peptide chemistry has made great progress, the frequent occurrence of aspartimide formation during peptide synthesis remains a formidable challenge. Aspartimide formation leads to low yields in addition to costly purification or even inaccessible peptide sequences. Here, we report an alternative approach to address this longstanding challenge of peptide synthesis by utilizing cyanosulfurylides to mask carboxylic acids by a stable C–C bond. These functional groups—formally zwitterionic species—are exceptionally stable to all common manipulations and impart improved solubility during synthesis. Deprotection is readily and rapidly achieved under aqueous conditions with electrophilic halogenating agents via a highly selective C–C bond cleavage reaction. This protecting group is employed for the synthesis of a range of peptides and proteins including teduglutide, ubiquitin, and the low-density lipoprotein class A. This protecting group strategy has the potential to overcome one of the most difficult aspects of modern peptide chemistry. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000403169Publication status
publishedExternal links
Journal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
Nature Publishing GroupOrganisational unit
03861 - Bode, Jeffrey W. / Bode, Jeffrey W.
Funding
169451 - Protein Synthesis with Chemoselective Ligations (SNF)
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Show all metadata
Citations
Cited 14 times in
Web of Science
Cited 16 times in
Scopus
ETH Bibliography
yes
Altmetrics