Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly
Abstract Peptide drugs have disadvantages such as low stability, short half-life and side effects, which limit their widespread use in clinical practice. Therefore, peptide drugs can be modified to improve these disadvantages. Numerous studies have shown that alkyl-modified peptide drugs can self-as...
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| Format: | Article |
| Language: | English |
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Springer
2024-03-01
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| Series: | Amino Acids |
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| Online Access: | https://doi.org/10.1007/s00726-023-03366-2 |
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| _version_ | 1846112449978171392 |
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| author | Xiufang Ding Yue Wang Sida Zhang Ruihua Zhang Dong Chen Changcai Liu Jianfu Xu Long Chen |
| author_facet | Xiufang Ding Yue Wang Sida Zhang Ruihua Zhang Dong Chen Changcai Liu Jianfu Xu Long Chen |
| author_sort | Xiufang Ding |
| collection | DOAJ |
| description | Abstract Peptide drugs have disadvantages such as low stability, short half-life and side effects, which limit their widespread use in clinical practice. Therefore, peptide drugs can be modified to improve these disadvantages. Numerous studies have shown that alkyl-modified peptide drugs can self-assemble to prolong the duration of efficacy and/or reduce side effects. However, the commonly used solid-phase synthesis method for alkyl-modified peptides is time-consuming. To overcome this, a simple reductive amination reaction was employed, which can directly graft the alkyl chain to the peptide sequence and effectively avoid stepwise synthesis from C- to N-terminal with amino acids. In this study, ω-conotoxin MVIIA was used as the peptide drug, while myristic aldehyde was used as the alkylating agent. To obtain the maximum productivity of modified peptides, the molar ratio of peptide MVIIA to myristic aldehyde in the reductive amination reaction was optimized. Furthermore, the peptide modification sites in this reaction were confirmed by secondary mass spectrometry analysis. Besides, alkyl-modified peptide MVIIA was able to form micelles by self-assembly and improved stability in serum, which was related to our previous work where myristoylated peptide MVIIA micelles can improve the drug stability. Finally, this study was intended to provide a methodological basis for modifying the alkyl chain of peptide drugs. |
| format | Article |
| id | doaj-art-e5dad2a2a44c4d12aaf9e62bd0a8b9ac |
| institution | Kabale University |
| issn | 1438-2199 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Amino Acids |
| spelling | doaj-art-e5dad2a2a44c4d12aaf9e62bd0a8b9ac2024-12-22T12:34:19ZengSpringerAmino Acids1438-21992024-03-0156111110.1007/s00726-023-03366-2Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assemblyXiufang Ding0Yue Wang1Sida Zhang2Ruihua Zhang3Dong Chen4Changcai Liu5Jianfu Xu6Long Chen7State Key Laboratory of NBC Protection for CivilianState Key Laboratory of NBC Protection for CivilianState Key Laboratory of NBC Protection for CivilianState Key Laboratory of NBC Protection for CivilianState Key Laboratory of NBC Protection for CivilianState Key Laboratory of NBC Protection for CivilianState Key Laboratory of NBC Protection for CivilianBeijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical TechnologyAbstract Peptide drugs have disadvantages such as low stability, short half-life and side effects, which limit their widespread use in clinical practice. Therefore, peptide drugs can be modified to improve these disadvantages. Numerous studies have shown that alkyl-modified peptide drugs can self-assemble to prolong the duration of efficacy and/or reduce side effects. However, the commonly used solid-phase synthesis method for alkyl-modified peptides is time-consuming. To overcome this, a simple reductive amination reaction was employed, which can directly graft the alkyl chain to the peptide sequence and effectively avoid stepwise synthesis from C- to N-terminal with amino acids. In this study, ω-conotoxin MVIIA was used as the peptide drug, while myristic aldehyde was used as the alkylating agent. To obtain the maximum productivity of modified peptides, the molar ratio of peptide MVIIA to myristic aldehyde in the reductive amination reaction was optimized. Furthermore, the peptide modification sites in this reaction were confirmed by secondary mass spectrometry analysis. Besides, alkyl-modified peptide MVIIA was able to form micelles by self-assembly and improved stability in serum, which was related to our previous work where myristoylated peptide MVIIA micelles can improve the drug stability. Finally, this study was intended to provide a methodological basis for modifying the alkyl chain of peptide drugs.https://doi.org/10.1007/s00726-023-03366-2Reductive aminationMVIIAConotoxinModificationSelf-assembly |
| spellingShingle | Xiufang Ding Yue Wang Sida Zhang Ruihua Zhang Dong Chen Changcai Liu Jianfu Xu Long Chen Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly Amino Acids Reductive amination MVIIA Conotoxin Modification Self-assembly |
| title | Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly |
| title_full | Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly |
| title_fullStr | Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly |
| title_full_unstemmed | Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly |
| title_short | Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly |
| title_sort | reductive amination of ω conotoxin mviia synthesis determination of modification sites and self assembly |
| topic | Reductive amination MVIIA Conotoxin Modification Self-assembly |
| url | https://doi.org/10.1007/s00726-023-03366-2 |
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