Translation of Deoxyribonucleic Acid into Synthetic Alpha Helical Peptides for Darwinian Evolution.

IF 8.5 Q1 CHEMISTRY, MULTIDISCIPLINARY
JACS Au Pub Date : 2024-10-02 eCollection Date: 2024-10-28 DOI:10.1021/jacsau.4c00738
Millicent Dockerill, Pramod M Sabale, Francesco Russo, Sofia Barluenga, Nicolas Winssinger
{"title":"Translation of Deoxyribonucleic Acid into Synthetic Alpha Helical Peptides for Darwinian Evolution.","authors":"Millicent Dockerill, Pramod M Sabale, Francesco Russo, Sofia Barluenga, Nicolas Winssinger","doi":"10.1021/jacsau.4c00738","DOIUrl":null,"url":null,"abstract":"<p><p>DNA-encoded libraries connect the phenotypes of synthetic molecules to a DNA barcode; however, most libraries do not tap into the potential of Darwinian evolution. Herein, we report a DNA-templated synthesis (DTS) architecture to make peptides that are stabilized into α-helical conformations via head-to-tail supramolecular cyclization. Using a pilot library targeting MDM2, we show that repeated screening can amplify a binder from the lowest abundance in the library to a ranking that correlates to binding affinity. The study also highlights the need to design libraries such that the chemistry avoids biases from the heterogeneous yield in DTS.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 10","pages":"4013-4022"},"PeriodicalIF":8.5000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522901/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACS Au","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/jacsau.4c00738","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/28 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

DNA-encoded libraries connect the phenotypes of synthetic molecules to a DNA barcode; however, most libraries do not tap into the potential of Darwinian evolution. Herein, we report a DNA-templated synthesis (DTS) architecture to make peptides that are stabilized into α-helical conformations via head-to-tail supramolecular cyclization. Using a pilot library targeting MDM2, we show that repeated screening can amplify a binder from the lowest abundance in the library to a ranking that correlates to binding affinity. The study also highlights the need to design libraries such that the chemistry avoids biases from the heterogeneous yield in DTS.

将脱氧核糖核酸转化为合成阿尔法螺旋肽,实现达尔文进化论。
DNA编码文库将合成分子的表型与DNA条形码连接起来;然而,大多数文库并没有挖掘达尔文进化论的潜力。在本文中,我们报告了一种DNA模板合成(DTS)结构,通过头尾超分子环化将多肽稳定为α螺旋构象。通过使用针对 MDM2 的试验文库,我们发现反复筛选可以将一个结合剂从文库中最低的丰度放大到与结合亲和力相关的等级。这项研究还强调了设计文库的必要性,这样才能避免 DTS 中异质产率造成的化学偏差。
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 求助全文
来源期刊
CiteScore
9.10
自引率
0.00%
发文量
0
审稿时长
10 weeks
×
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:481959085
Book学术官方微信