Revisiting NO2 as Protecting Group of Arginine in Solid-Phase Peptide Synthesis

The protection of side-chain arginine in solid-phase peptide synthesis requires attention since current protecting groups have several drawbacks. Herein, the NO2 group, which is scarcely used, has been revisited. This work shows that it prevents the formation of δ-lactam, the most severe side-reacti...

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Detalhes bibliográficos
Autores: Alhassan, Mahama, Kumar, Ashish, Lopez, John, Albericio, Fernando, de la Torre, Beatriz G.
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/220110
Acesso em linha:http://hdl.handle.net/10261/220110
Access Level:Acceso aberto
Palavra-chave:Sonochemistry
δ-lactam formation
Microwave
Protecting group
Orthogonal protection
NBP
Side-reaction
solid-phase peptide synthesi
Descrição
Resumo:The protection of side-chain arginine in solid-phase peptide synthesis requires attention since current protecting groups have several drawbacks. Herein, the NO2 group, which is scarcely used, has been revisited. This work shows that it prevents the formation of δ-lactam, the most severe side-reaction during the incorporation of Arg. Moreover, it is stable in solution for long periods and can be removed in an easy-to-understand manner. Thus, this protecting group can be removed while the protected peptide is still anchored to the resin, with SnCl2 as reducing agent in mild acid conditions using 2-MeTHF as solvent at 55 °C. Furthermore, we demonstrate that sonochemistry can facilitate the removal of NO2 from multiple Arg-containing peptides.