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。

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
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引用次数: 0

摘要

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

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.

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CiteScore
9.10
自引率
0.00%
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审稿时长
10 weeks
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