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 : 2024-10-30 DOI:10.1039/d4ob01436g

Sunbum Kwon , Vasily Morozov , Lingfei Wang , Pradeep K. Mandal , Stéphane Chaignepain , Céline Douat , Ivan Huc

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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.

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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。

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来源期刊

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： Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.