The DOI matches its Crossref record; 386 of the 386 references it cites were found in a registry or an index.
Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations
Abstract
The native chemical ligation reaction (NCL) involves reacting a C-terminal peptide thioester with an N-terminal cysteinyl peptide to produce a native peptide bond between the two fragments. This reaction has considerably extended the size of polypeptides and proteins that can be produced by total synthesis and has also numerous applications in bioconjugation, polymer synthesis, material science, and micro- and nanotechnology research. The aim of the present review is to provide a thorough mechanistic overview of NCL and extended methods. The most relevant properties of peptide thioesters, Cys peptides, and common solvents, reagents, additives, and catalysts used for these ligations are presented. Mechanisms, selectivity and reactivity are, whenever possible, discussed through the insights of computational and physical chemistry studies. The inherent limitations of NCL are discussed with insights from the mechanistic standpoint. This review also presents a palette of O, S-, N, S-, or N, Se-acyl shift systems as thioester or selenoester surrogates and discusses the special molecular features that govern reactivity in each case. Finally, the various thiol-based auxiliaries and thiol or selenol amino acid surrogates that have been developed so far are discussed with a special focus on the mechanism of long-range N, S-acyl migrations and selective dechalcogenation reactions.
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Cites
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Synthesis of proteins by automated flow chemistry
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Uncovering post-translational modification-associated protein–protein interactions
Wang, S., Osgood, A. O., & Chatterjee, A. (2022) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2022.102352 · Cited by 153
Synthesis and applications of mirror-image proteins
Harrison, K., Mackay, A. S., Kambanis, L., Maxwell, J. W. C., & Payne, R. J. (2023) · Nature Reviews Chemistry · doi:10.1038/s41570-023-00493-y · Cited by 104
Main methods and tools for peptide development based on protein-protein interactions (PPIs)
Baeza, J., Bedoya, M., Cruz, P., Ojeda, P., Adasme-Carreño, F., Cerda, O., & González, W. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151623 · Cited by 8
Metadata
- Authors
- Agouridas, V., El Mahdi, O., Diemer, V., Cargoët, M., Monbaliu, J.-C. M., & Melnyk, O.
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-05-03
- Volume
- 119
- Issue
- 12
- Pages
- 7328-7443
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- OpenAlex
- W2943553643
- Cited by
- 650
- References
- 386
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- closed
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- Agouridas, V., El Mahdi, O., Diemer, V., Cargoët, M., Monbaliu, J.-C. M., & Melnyk, O. (2019). Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations. Chemical Reviews. https://doi.org/10.1021/acs.chemrev.8b00712
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