Selective Activation of Peptide‐Thioester Precursors for Templated Native Chemical Ligations
Abstract: Chemical protein synthesis enables access to proteins that would otherwise be difficult or impossible to obtain with traditional means such as recombinant expression. Chemoselective ligations provide the ability to join peptide segments prepared by solid‐phase peptide synthesis. While native chemical ligation (NCL) is widely used, it is limited by the need for C‐terminal thioesters with suitable reaction kinetics, properly placed native Cys or thiolated derivatives, and peptide segment solubility at low mM concentrations. Moreover, repetitive purifications to isolate ligated products are often yield‐sapping, hampering efficiency and progress. In this work, we demonstrate the use of Controlled Activation of Peptides for Templated NCL (CAPTN). This traceless multi‐segment templated NCL approach permits the one‐pot synthesis of proteins by harnessing selective thioester activation and orthogonal conjugation chemistries to favor formation of the full‐length ligated product while minimizing side reactions. Importantly, CAPTN provides kinetic enhancements allowing ligations at sterically hindered junctions and low peptide concentrations. Additionally, this one‐pot approach removes the need for intermediate purification. We report the synthesis of two E. coli ribosomal subunits S16 and S17 enabled by the chemical tools described herein. We anticipate that CAPTN will expedite the synthesis of valuable proteins and expand on templated approaches for chemical protein synthesis.
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Bibliographic citation
-
Selective Activation of Peptide‐Thioester Precursors for Templated Native Chemical Ligations ; day:24 ; month:10 ; year:2024 ; extent:12
Angewandte Chemie ; (24.10.2024) (gesamt 12)
- Creator
-
Spaltenstein, Paul
Giesler, Riley J.
Scherer, Samuel R.
Erickson, Patrick W.
Kay, Michael S.
- DOI
-
10.1002/ange.202413644
- URN
-
urn:nbn:de:101:1-2410251446212.625526922044
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
15.08.2025, 7:20 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Spaltenstein, Paul
- Giesler, Riley J.
- Scherer, Samuel R.
- Erickson, Patrick W.
- Kay, Michael S.
Other Objects (12)
Selective Activation of Peptide‐Thioester Precursors for Templated Native Chemical Ligations
RNA‐Templated Peptide Bond Formation Promotes L‐Homochirality
Peptide-templated acyl transfer as novel strategy for live cell imaging
Late metabolic precursors for selective aromatic residue labeling
Synthesis of hypermodified nucleosides and examination of nucleic acid templated stereoselective peptide formation in an RNA-peptide world
Templated organic synthesis
Infant selective attention to native and non-native audiovisual speech
Selective Behaviour of Honeybees in Acquiring European Propolis Plant Precursors
Amyloid-beta Peptide unterstützen die native Immunabwehr
Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures
Biomimetic Identification of Phase-Selective Peptide-Additives
Switchable Electrostatically Templated Polymerization
Selective Activation of Peptide‐Thioester Precursors for Templated Native Chemical Ligations
RNA‐Templated Peptide Bond Formation Promotes L‐Homochirality
Peptide-templated acyl transfer as novel strategy for live cell imaging
Late metabolic precursors for selective aromatic residue labeling
Synthesis of hypermodified nucleosides and examination of nucleic acid templated stereoselective peptide formation in an RNA-peptide world
Templated organic synthesis
Infant selective attention to native and non-native audiovisual speech
Selective Behaviour of Honeybees in Acquiring European Propolis Plant Precursors
Amyloid-beta Peptide unterstützen die native Immunabwehr
Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures
Biomimetic Identification of Phase-Selective Peptide-Additives
Switchable Electrostatically Templated Polymerization
Selective Activation of Peptide‐Thioester Precursors for Templated Native Chemical Ligations
RNA‐Templated Peptide Bond Formation Promotes L‐Homochirality
Peptide-templated acyl transfer as novel strategy for live cell imaging
Late metabolic precursors for selective aromatic residue labeling
Synthesis of hypermodified nucleosides and examination of nucleic acid templated stereoselective peptide formation in an RNA-peptide world
Templated organic synthesis
Infant selective attention to native and non-native audiovisual speech
Selective Behaviour of Honeybees in Acquiring European Propolis Plant Precursors
Amyloid-beta Peptide unterstützen die native Immunabwehr
Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures
Biomimetic Identification of Phase-Selective Peptide-Additives