A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide

Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selectiv...

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Detalles Bibliográficos
Autores principales: Qiu, Zhonghao, Dai, Xiandong, Fan, Chongxu, Cao, Ying, Lv, Zirui, Liang, Xingyong, Meng, Fanhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9919235/
https://www.ncbi.nlm.nih.gov/pubmed/36770675
http://dx.doi.org/10.3390/molecules28031007
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author Qiu, Zhonghao
Dai, Xiandong
Fan, Chongxu
Cao, Ying
Lv, Zirui
Liang, Xingyong
Meng, Fanhua
author_facet Qiu, Zhonghao
Dai, Xiandong
Fan, Chongxu
Cao, Ying
Lv, Zirui
Liang, Xingyong
Meng, Fanhua
author_sort Qiu, Zhonghao
collection PubMed
description Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively.
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spelling pubmed-99192352023-02-12 A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide Qiu, Zhonghao Dai, Xiandong Fan, Chongxu Cao, Ying Lv, Zirui Liang, Xingyong Meng, Fanhua Molecules Article Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively. MDPI 2023-01-19 /pmc/articles/PMC9919235/ /pubmed/36770675 http://dx.doi.org/10.3390/molecules28031007 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Qiu, Zhonghao
Dai, Xiandong
Fan, Chongxu
Cao, Ying
Lv, Zirui
Liang, Xingyong
Meng, Fanhua
A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide
title A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide
title_full A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide
title_fullStr A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide
title_full_unstemmed A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide
title_short A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide
title_sort new regioselective synthesis of the cysteine-rich peptide linaclotide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9919235/
https://www.ncbi.nlm.nih.gov/pubmed/36770675
http://dx.doi.org/10.3390/molecules28031007
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