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Coupling of sterically demanding peptides by β-thiolactone-mediated native chemical ligation
The ligation of sterically demanding peptidyl sites such as those involving Val–Val and Val–Pro linkages has proven to be extremely challenging with conventional NCL methods that rely on exogenous thiol additives. Herein, we report an efficient β-thiolactone-mediated additive-free NCL protocol that...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892351/ https://www.ncbi.nlm.nih.gov/pubmed/29675245 http://dx.doi.org/10.1039/c7sc04744d |
Sumario: | The ligation of sterically demanding peptidyl sites such as those involving Val–Val and Val–Pro linkages has proven to be extremely challenging with conventional NCL methods that rely on exogenous thiol additives. Herein, we report an efficient β-thiolactone-mediated additive-free NCL protocol that enables the establishment of these connections in good yield. The rapid NCL was followed by in situ desulfurization. Reaction rates between β-thiolactones and conventional thioesters towards NCL were also investigated, and direct aminolysis was ruled out as a possible pathway. Finally, the potent cytotoxic cyclic-peptide axinastatin 1 has been prepared using the developed methodology. |
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