2-Methoxy-4-methylsulfinylbenzyl Alcohol as a Safety-Catch Linker for the Fmoc/tBu Solid-Phase Peptide Synthesis Strategy

Fmoc and Boc group are the two main groups used to protect the α-amino function in Solid-Phase Peptide Synthesis (SPPS). In this regard, the use of the Mmsb linker allows the combination of these two groups. Peptide-O-Mmsb-Resin is stable to the piperidine and trifluoroacetic acid (TFA) treatment us...

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Bibliographic Details
Authors: Nandhini, K. P., Albericio, Fernando, de la Torre, Beatriz G.
Format: article
Status:Versión aceptada para publicación
Publication Date:2022
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/310408
Online Access:http://hdl.handle.net/10261/310408
https://api.elsevier.com/content/abstract/scopus_id/85135232357
Access Level:Open access
Keyword:Solid-Phase Peptide Synthesis (SPPS)
Trifluoroacetic acid (TFA)
http://metadata.un.org/sdg/3
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Description
Summary:Fmoc and Boc group are the two main groups used to protect the α-amino function in Solid-Phase Peptide Synthesis (SPPS). In this regard, the use of the Mmsb linker allows the combination of these two groups. Peptide-O-Mmsb-Resin is stable to the piperidine and trifluoroacetic acid (TFA) treatment used to remove Fmoc and Boc, respectively. The peptide is detached in a two-step protocol, namely reduction of the sulfoxide to the sulfide with Me3SiCl and Ph3P, and then treatment with TFA. The advantage of this strategy has been demonstrated by the following: preparation of peptide with no diketopiperazine formation in sequences prone to this side reaction; on-resin cyclization without the concourse of common organic reagents such as Pd(0) but of difficult use in a biological laboratory; and on-resin disulfide formation in a total side-chain unprotected peptide. The use of Mmsb linker together with Msib (4-(methylsulfinyl)benzyl) and Msbh (4,4'-bis(methylsulfinyl)benzhydryl) described in the accompanying manuscript add a fourth dimension to the SPPS protecting group scheme.