用β-环糊精直接连续流合成两种困难多肽

IF 3.6 2区 化学 Q1 CHEMISTRY, ORGANIC
Szebasztián Szaniszló, Gitta Schlosser, Viktor Farkas and András Perczel*, 
{"title":"用β-环糊精直接连续流合成两种困难多肽","authors":"Szebasztián Szaniszló,&nbsp;Gitta Schlosser,&nbsp;Viktor Farkas and András Perczel*,&nbsp;","doi":"10.1021/acs.joc.4c0158910.1021/acs.joc.4c01589","DOIUrl":null,"url":null,"abstract":"<p >This study focuses on investigating the use of β-cyclodextrin (β-CyD) derivatives as additives in continuous flow peptide synthesis, with particular emphasis on challenging sequences such as the Jung-Redemann decapeptide and the 42-residue amyloid β polypeptide [Aβ(1–42)]. The efficacy of the OH-free β-CyD and two of its derivatives (Ac-β-CyD and HP-β-CyD) is compared with alternative, state-of-the-art synthetic methods, including the widely used and recently improved pseudoproline monomer technique, e.g., Ser(ΨPro). Our results show that the use of β-CyD as an additive results in a significant (8–19%) increase in the purity of the crude polypeptide compared to that determined by our reference method. The chromatograms determined by LC-MS were deconvoluted to estimate the more precise purity of the crude products, and we found that the improvement is greater when the free OH β-CyD is used and moderate when the acetyl-β-CyD or the 2-hydroxypropyl-β-CyD derivatives are used. We have found that the free CyD gives an improvement comparable to that achieved with the Ser(ΨPro) derivative.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"89 24","pages":"18039–18046 18039–18046"},"PeriodicalIF":3.6000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Direct Continuous Flow Synthesis of Two Difficult Polypeptides Using β-Cyclodextrins\",\"authors\":\"Szebasztián Szaniszló,&nbsp;Gitta Schlosser,&nbsp;Viktor Farkas and András Perczel*,&nbsp;\",\"doi\":\"10.1021/acs.joc.4c0158910.1021/acs.joc.4c01589\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >This study focuses on investigating the use of β-cyclodextrin (β-CyD) derivatives as additives in continuous flow peptide synthesis, with particular emphasis on challenging sequences such as the Jung-Redemann decapeptide and the 42-residue amyloid β polypeptide [Aβ(1–42)]. The efficacy of the OH-free β-CyD and two of its derivatives (Ac-β-CyD and HP-β-CyD) is compared with alternative, state-of-the-art synthetic methods, including the widely used and recently improved pseudoproline monomer technique, e.g., Ser(ΨPro). Our results show that the use of β-CyD as an additive results in a significant (8–19%) increase in the purity of the crude polypeptide compared to that determined by our reference method. The chromatograms determined by LC-MS were deconvoluted to estimate the more precise purity of the crude products, and we found that the improvement is greater when the free OH β-CyD is used and moderate when the acetyl-β-CyD or the 2-hydroxypropyl-β-CyD derivatives are used. We have found that the free CyD gives an improvement comparable to that achieved with the Ser(ΨPro) derivative.</p>\",\"PeriodicalId\":57,\"journal\":{\"name\":\"Journal of Organic Chemistry\",\"volume\":\"89 24\",\"pages\":\"18039–18046 18039–18046\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-11-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Organic Chemistry\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.joc.4c01589\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Organic Chemistry","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.joc.4c01589","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0

摘要

本研究重点研究了β-环糊精(β- cyd)衍生物作为添加剂在连续流动肽合成中的应用,特别强调了具有挑战性的序列,如Jung-Redemann十肽和42-残基淀粉样β多肽[Aβ(1-42)]。不含oh的β-CyD及其两个衍生物(Ac-β-CyD和HP-β-CyD)的功效与其他最先进的合成方法进行了比较,包括广泛使用和最近改进的假脯氨酸单体技术,例如Ser(ΨPro)。我们的研究结果表明,与我们的参考方法相比,使用β-CyD作为添加剂可以显著提高粗多肽的纯度(8-19%)。对LC-MS测定的色谱进行反旋,以估计更精确的粗产物纯度,我们发现当使用游离OH β-CyD时,提高幅度较大,当使用乙酰-β-CyD或2-羟丙基-β-CyD衍生物时,提高幅度较小。我们发现,自由CyD提供了与Ser(ΨPro)衍生物相当的改进。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Direct Continuous Flow Synthesis of Two Difficult Polypeptides Using β-Cyclodextrins

Direct Continuous Flow Synthesis of Two Difficult Polypeptides Using β-Cyclodextrins

This study focuses on investigating the use of β-cyclodextrin (β-CyD) derivatives as additives in continuous flow peptide synthesis, with particular emphasis on challenging sequences such as the Jung-Redemann decapeptide and the 42-residue amyloid β polypeptide [Aβ(1–42)]. The efficacy of the OH-free β-CyD and two of its derivatives (Ac-β-CyD and HP-β-CyD) is compared with alternative, state-of-the-art synthetic methods, including the widely used and recently improved pseudoproline monomer technique, e.g., Ser(ΨPro). Our results show that the use of β-CyD as an additive results in a significant (8–19%) increase in the purity of the crude polypeptide compared to that determined by our reference method. The chromatograms determined by LC-MS were deconvoluted to estimate the more precise purity of the crude products, and we found that the improvement is greater when the free OH β-CyD is used and moderate when the acetyl-β-CyD or the 2-hydroxypropyl-β-CyD derivatives are used. We have found that the free CyD gives an improvement comparable to that achieved with the Ser(ΨPro) derivative.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Organic Chemistry
Journal of Organic Chemistry 化学-有机化学
CiteScore
6.20
自引率
11.10%
发文量
1467
审稿时长
2 months
期刊介绍: Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信