翻译后修饰的Max转录因子的一锅全合成揭示了DNA结合中的ser -磷酸化和lys -乙酰化串音

IF 5 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2025-03-31 DOI:10.1021/acs.orglett.5c00978

Raj V. Nithun, Shada Khoury, Muhammad Jbara

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引用次数: 0

摘要

我们报道了一锅全合成转录因子Max连续七个步骤，从三个肽段开始，并采用天然化学连接。所开发的合成方法有助于在数小时内以优异的产率生成具有定义转化的均匀Max类似物，使我们能够探测ser -磷酸化和lys -乙酰化之间的串音对Max函数的影响。我们的研究结果表明，这些翻译后修饰可能通过破坏基本的Max-DNA相互作用来显著抑制dna结合活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

One-Pot Total Synthesis of a Post-translationally Modified Max Transcription Factor Sheds Light on Ser-Phosphorylation and Lys-Acetylation Crosstalk in DNA Binding

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One-Pot Total Synthesis of a Post-translationally Modified Max Transcription Factor Sheds Light on Ser-Phosphorylation and Lys-Acetylation Crosstalk in DNA Binding

We report a one-pot total synthesis of the transcription factor Max in seven consecutive steps, starting from three peptide segments and employing native chemical ligation. The developed synthesis facilitates the generation of homogeneous Max analogues bearing defined transformations within hours in excellent yields, enabling us to probe the effect of the crosstalk between Ser-phosphorylation and Lys-acetylation on the Max function. Our findings reveal that these post-translational modifications significantly inhibit DNA-binding activity, potentially by disrupting essential Max–DNA interactions.

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.