An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds

Disulfide bonds are crucial for stabilizing bioactive peptides such as conotoxins. We have developed a method for synthesizing conotoxins with three disulfide bonds using Mob, Trt, and Acm protection groups for regionally selective synthesis. This approach enabled the efficient synthesis of peptides...

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Main Authors: Hengyu Zhang, Lai Yue Chan, Huanhuan Zhang, Tao Jiang, David J. Craik, Wenqing Cai, Rilei Yu
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/23/4/168
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author Hengyu Zhang
Lai Yue Chan
Huanhuan Zhang
Tao Jiang
David J. Craik
Wenqing Cai
Rilei Yu
author_facet Hengyu Zhang
Lai Yue Chan
Huanhuan Zhang
Tao Jiang
David J. Craik
Wenqing Cai
Rilei Yu
author_sort Hengyu Zhang
collection DOAJ
description Disulfide bonds are crucial for stabilizing bioactive peptides such as conotoxins. We have developed a method for synthesizing conotoxins with three disulfide bonds using Mob, Trt, and Acm protection groups for regionally selective synthesis. This approach enabled the efficient synthesis of peptides with the desired disulfide bond connectivities independent of their sequences. Using our strategy, we synthesized five conotoxins, achieving yields of 20–30%. The results demonstrate the potential of our method for synthesizing complex peptides with multiple disulfide bonds.
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publisher MDPI AG
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series Marine Drugs
spelling doaj-art-eccff36debc74da0b7eadc30c00a77962025-08-20T02:18:19ZengMDPI AGMarine Drugs1660-33972025-04-0123416810.3390/md23040168An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide BondsHengyu Zhang0Lai Yue Chan1Huanhuan Zhang2Tao Jiang3David J. Craik4Wenqing Cai5Rilei Yu6Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaInstitute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD 4072, AustraliaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaInstitute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD 4072, AustraliaShandong Academy of Pharmaceutical Sciences, Jinan 250100, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaDisulfide bonds are crucial for stabilizing bioactive peptides such as conotoxins. We have developed a method for synthesizing conotoxins with three disulfide bonds using Mob, Trt, and Acm protection groups for regionally selective synthesis. This approach enabled the efficient synthesis of peptides with the desired disulfide bond connectivities independent of their sequences. Using our strategy, we synthesized five conotoxins, achieving yields of 20–30%. The results demonstrate the potential of our method for synthesizing complex peptides with multiple disulfide bonds.https://www.mdpi.com/1660-3397/23/4/168orthogonal oxidation methodthree disulfide bondsconotoxins
spellingShingle Hengyu Zhang
Lai Yue Chan
Huanhuan Zhang
Tao Jiang
David J. Craik
Wenqing Cai
Rilei Yu
An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds
Marine Drugs
orthogonal oxidation method
three disulfide bonds
conotoxins
title An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds
title_full An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds
title_fullStr An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds
title_full_unstemmed An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds
title_short An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds
title_sort orthogonal protection strategy for the synthesis of conotoxins containing three disulfide bonds
topic orthogonal oxidation method
three disulfide bonds
conotoxins
url https://www.mdpi.com/1660-3397/23/4/168
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