Interrogating the potential of helical aromatic foldamers for protein recognition.

IF 2.9 3区 化学 Q1 CHEMISTRY, ORGANIC Organic & Biomolecular Chemistry Pub Date : 2024-11-06 DOI:10.1039/d4ob01436g
Sunbum Kwon, Vasily Morozov, Lingfei Wang, Pradeep K Mandal, Stéphane Chaignepain, Céline Douat, Ivan Huc
{"title":"Interrogating the potential of helical aromatic foldamers for protein recognition.","authors":"Sunbum Kwon, Vasily Morozov, Lingfei Wang, Pradeep K Mandal, Stéphane Chaignepain, Céline Douat, Ivan Huc","doi":"10.1039/d4ob01436g","DOIUrl":null,"url":null,"abstract":"<p><p>A biotinylated helical aromatic oligoamide foldamer equivalent in size to a 24mer peptide was designed without any prejudice other than to display various polar and hydrophobic side chains at its surface. It was synthesized on solid phase, its <i>P</i>- and <i>M</i>-helical conformers were separated by HPLC on a chiral stationary phase, and the solid state structure of a non-biotinylated analogue was elucidated by X-ray crystallography. Pull-down experiments from a yeast cell lysate using the foldamer as a bait followed by proteomic analysis revealed potential protein binding partners. Three of these proteins were recombinantly expressed. Biolayer interferometry showed submicromolar binding demonstrating the potential of a given foldamer to have affinity for certain proteins in the absence of design considerations. Yet, binding selectivity was low in all three cases since both <i>P</i>- and <i>M</i>-conformers bound to the proteins with similar affinities.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic & Biomolecular Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1039/d4ob01436g","RegionNum":3,"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

Abstract

A biotinylated helical aromatic oligoamide foldamer equivalent in size to a 24mer peptide was designed without any prejudice other than to display various polar and hydrophobic side chains at its surface. It was synthesized on solid phase, its P- and M-helical conformers were separated by HPLC on a chiral stationary phase, and the solid state structure of a non-biotinylated analogue was elucidated by X-ray crystallography. Pull-down experiments from a yeast cell lysate using the foldamer as a bait followed by proteomic analysis revealed potential protein binding partners. Three of these proteins were recombinantly expressed. Biolayer interferometry showed submicromolar binding demonstrating the potential of a given foldamer to have affinity for certain proteins in the absence of design considerations. Yet, binding selectivity was low in all three cases since both P- and M-conformers bound to the proteins with similar affinities.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
探究螺旋芳香折叠器识别蛋白质的潜力。
除了在其表面显示各种极性和疏水侧链外,我们还设计了一种生物素化的螺旋芳香族寡酰胺折叠聚合物,其大小相当于 24 聚肽。该产品在固相上合成,其 P-和 M-螺旋构象在手性固定相上通过高效液相色谱进行分离,并通过 X 射线晶体学阐明了非生物素化类似物的固态结构。以折叠酶为诱饵从酵母细胞裂解物中进行拉取实验,然后进行蛋白质组分析,发现了潜在的蛋白质结合伙伴。其中三种蛋白质被重组表达。生物层干涉测量法显示了亚摩尔级的结合力,这表明在没有设计考虑的情况下,特定的折叠聚合体对某些蛋白质具有亲和力。然而,这三种情况下的结合选择性都很低,因为 P 型和 M 型折叠体与蛋白质的结合亲和力相似。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry 化学-有机化学
CiteScore
5.50
自引率
9.40%
发文量
1056
审稿时长
1.3 months
期刊介绍: The international home of synthetic, physical and biomolecular organic chemistry.
期刊最新文献
Back cover Interrogating the potential of helical aromatic foldamers for protein recognition. Synthesis of the 5/5-spiroindimicin alkaloids: development of a general synthetic approach and biological investigations. Electrochemical one-pot cascade synthesis of thio(seleno)cyanato-substituted thiazolidine-2-imines without external electrolyte. Novel electron donor-acceptor (EDA) complex promoted arylation of 2-oxo-2H-chromene-3-carbonitriles under visible light irradiation.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1