Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis

[Image: see text] DKP (diketopiperazine) formation is a ubiquitous side reaction in SPPS (solid-phase peptide synthesis) that is highly sequence-dependent. Secondary amino acids are extremely prone to host such a side reaction. DKP formation is predominantly induced at the Fmoc (fluorenylmethyloxyca...

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Autores principales: Yang, Yi, Hansen, Lena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016848/
https://www.ncbi.nlm.nih.gov/pubmed/35449974
http://dx.doi.org/10.1021/acsomega.2c00214
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author Yang, Yi
Hansen, Lena
author_facet Yang, Yi
Hansen, Lena
author_sort Yang, Yi
collection PubMed
description [Image: see text] DKP (diketopiperazine) formation is a ubiquitous side reaction in SPPS (solid-phase peptide synthesis) that is highly sequence-dependent. Secondary amino acids are extremely prone to host such a side reaction. DKP formation is predominantly induced at the Fmoc (fluorenylmethyloxycarbonyl)-removal step mediated by a secondary amine, which conventionally employs piperidine/DMF (dimethylformamide). In this study, alternative Fmoc-removal solution 2% DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)/5% piperazine/NMP (N-methyl-2-pyrrolidone) led to drastic DKP reduction relative to 20% piperidine/DMF.
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spelling pubmed-90168482022-04-20 Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis Yang, Yi Hansen, Lena ACS Omega [Image: see text] DKP (diketopiperazine) formation is a ubiquitous side reaction in SPPS (solid-phase peptide synthesis) that is highly sequence-dependent. Secondary amino acids are extremely prone to host such a side reaction. DKP formation is predominantly induced at the Fmoc (fluorenylmethyloxycarbonyl)-removal step mediated by a secondary amine, which conventionally employs piperidine/DMF (dimethylformamide). In this study, alternative Fmoc-removal solution 2% DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)/5% piperazine/NMP (N-methyl-2-pyrrolidone) led to drastic DKP reduction relative to 20% piperidine/DMF. American Chemical Society 2022-03-29 /pmc/articles/PMC9016848/ /pubmed/35449974 http://dx.doi.org/10.1021/acsomega.2c00214 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Yang, Yi
Hansen, Lena
Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis
title Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis
title_full Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis
title_fullStr Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis
title_full_unstemmed Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis
title_short Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis
title_sort optimized fmoc-removal strategy to suppress the traceless and conventional diketopiperazine formation in solid-phase peptide synthesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016848/
https://www.ncbi.nlm.nih.gov/pubmed/35449974
http://dx.doi.org/10.1021/acsomega.2c00214
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