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Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam

In the last couple of decades, technologies and strategies for peptide synthesis have advanced rapidly. Although solid-phase peptide synthesis (SPPS) and liquid-phase peptide synthesis (LPPS) have contributed significantly to the development of the field, there have been remaining challenges for C-t...

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Autores principales: Nakahara, Hiroki, Sennari, Goh, Noguchi, Yoshihiko, Hirose, Tomoyasu, Sunazuka, Toshiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306108/
https://www.ncbi.nlm.nih.gov/pubmed/37389244
http://dx.doi.org/10.1039/d3sc01432k
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author Nakahara, Hiroki
Sennari, Goh
Noguchi, Yoshihiko
Hirose, Tomoyasu
Sunazuka, Toshiaki
author_facet Nakahara, Hiroki
Sennari, Goh
Noguchi, Yoshihiko
Hirose, Tomoyasu
Sunazuka, Toshiaki
author_sort Nakahara, Hiroki
collection PubMed
description In the last couple of decades, technologies and strategies for peptide synthesis have advanced rapidly. Although solid-phase peptide synthesis (SPPS) and liquid-phase peptide synthesis (LPPS) have contributed significantly to the development of the field, there have been remaining challenges for C-terminal modifications of peptide compounds in SPPS and LPPS. Orthogonal to the current standard approach that relies on installation of a carrier molecule at the C-terminus of amino acids, we developed a new hydrophobic-tag carbonate reagent which facilitated robust preparation of nitrogen-tag-supported peptide compounds. This auxiliary was easily installed on a variety of amino acids including oligopeptides that have a broad range of noncanonical residues, allowing simple purification of the products by crystallization and filtration. We demonstrated a de novo solid/hydrophobic-tag relay synthesis (STRS) strategy using the nitrogen-bound auxiliary for total synthesis of calpinactam.
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spelling pubmed-103061082023-06-29 Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam Nakahara, Hiroki Sennari, Goh Noguchi, Yoshihiko Hirose, Tomoyasu Sunazuka, Toshiaki Chem Sci Chemistry In the last couple of decades, technologies and strategies for peptide synthesis have advanced rapidly. Although solid-phase peptide synthesis (SPPS) and liquid-phase peptide synthesis (LPPS) have contributed significantly to the development of the field, there have been remaining challenges for C-terminal modifications of peptide compounds in SPPS and LPPS. Orthogonal to the current standard approach that relies on installation of a carrier molecule at the C-terminus of amino acids, we developed a new hydrophobic-tag carbonate reagent which facilitated robust preparation of nitrogen-tag-supported peptide compounds. This auxiliary was easily installed on a variety of amino acids including oligopeptides that have a broad range of noncanonical residues, allowing simple purification of the products by crystallization and filtration. We demonstrated a de novo solid/hydrophobic-tag relay synthesis (STRS) strategy using the nitrogen-bound auxiliary for total synthesis of calpinactam. The Royal Society of Chemistry 2023-05-01 /pmc/articles/PMC10306108/ /pubmed/37389244 http://dx.doi.org/10.1039/d3sc01432k Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Nakahara, Hiroki
Sennari, Goh
Noguchi, Yoshihiko
Hirose, Tomoyasu
Sunazuka, Toshiaki
Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam
title Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam
title_full Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam
title_fullStr Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam
title_full_unstemmed Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam
title_short Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam
title_sort development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306108/
https://www.ncbi.nlm.nih.gov/pubmed/37389244
http://dx.doi.org/10.1039/d3sc01432k
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