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Acetyl group for proper protection of β-sugar-amino acids used in SPPS
The synthesis of d-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Vienna
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514111/ https://www.ncbi.nlm.nih.gov/pubmed/37340192 http://dx.doi.org/10.1007/s00726-023-03278-1 |
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author | Varga, István Goldschmidt Gőz, Viktória Pintér, István Csámpai, Antal Perczel, András |
author_facet | Varga, István Goldschmidt Gőz, Viktória Pintér, István Csámpai, Antal Perczel, András |
author_sort | Varga, István |
collection | PubMed |
description | The synthesis of d-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc-GlcAPC(Ac)-OH, β-SAAs consisting of only 4–5 synthetic steps. Their active ester and amide bond formation with glycine methyl ester (H-Gly-OMe) was completed and monitored by (1)H NMR. The stability of the pyranoid OHs protecting the acetyl groups was investigated under three different Fmoc cleavage conditions and was found to be satisfactory even at high piperidine concentration (e.g. 40%). We designed a SPPS protocol using Fmoc-GlcAPC(Ac)-OH to produce model peptides Gly-β-SAA-Gly as well as Gly-β-SAA-β-SAA-Gly with high coupling efficiency. The products were deacetylated using the Zemplén method, which allows the hydrophilicity of a building block and/or chimera to be fine-tuned, even after the polypeptide chain has already been synthesized. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00726-023-03278-1. |
format | Online Article Text |
id | pubmed-10514111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Vienna |
record_format | MEDLINE/PubMed |
spelling | pubmed-105141112023-09-23 Acetyl group for proper protection of β-sugar-amino acids used in SPPS Varga, István Goldschmidt Gőz, Viktória Pintér, István Csámpai, Antal Perczel, András Amino Acids Original Article The synthesis of d-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc-GlcAPC(Ac)-OH, β-SAAs consisting of only 4–5 synthetic steps. Their active ester and amide bond formation with glycine methyl ester (H-Gly-OMe) was completed and monitored by (1)H NMR. The stability of the pyranoid OHs protecting the acetyl groups was investigated under three different Fmoc cleavage conditions and was found to be satisfactory even at high piperidine concentration (e.g. 40%). We designed a SPPS protocol using Fmoc-GlcAPC(Ac)-OH to produce model peptides Gly-β-SAA-Gly as well as Gly-β-SAA-β-SAA-Gly with high coupling efficiency. The products were deacetylated using the Zemplén method, which allows the hydrophilicity of a building block and/or chimera to be fine-tuned, even after the polypeptide chain has already been synthesized. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00726-023-03278-1. Springer Vienna 2023-06-21 2023 /pmc/articles/PMC10514111/ /pubmed/37340192 http://dx.doi.org/10.1007/s00726-023-03278-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Varga, István Goldschmidt Gőz, Viktória Pintér, István Csámpai, Antal Perczel, András Acetyl group for proper protection of β-sugar-amino acids used in SPPS |
title | Acetyl group for proper protection of β-sugar-amino acids used in SPPS |
title_full | Acetyl group for proper protection of β-sugar-amino acids used in SPPS |
title_fullStr | Acetyl group for proper protection of β-sugar-amino acids used in SPPS |
title_full_unstemmed | Acetyl group for proper protection of β-sugar-amino acids used in SPPS |
title_short | Acetyl group for proper protection of β-sugar-amino acids used in SPPS |
title_sort | acetyl group for proper protection of β-sugar-amino acids used in spps |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514111/ https://www.ncbi.nlm.nih.gov/pubmed/37340192 http://dx.doi.org/10.1007/s00726-023-03278-1 |
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