Cover Feature: Recognition of ASF1 by Using Hydrocarbon-Constrained Peptides (ChemBioChem 7/2019)
Cover Feature: Recognition of ASF1 by Using Hydrocarbon-Constrained Peptides (ChemBioChem 7/2019)
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封面专题：使用碳氢化合物限制肽识别 ASF1 (ChemBioChem 7/2019)
DOI：
10.1002/cbic.201900132
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发表时间：
2019
期刊：
影响因子：
3.2
通讯作者：
Bakail M
中科院分区：
文献类型：
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作者：
Bakail M
抑制组蛋白H3-ASF 1（抗沉默功能1）蛋白质-蛋白质相互作用（PPI）代表了治疗多种癌症的潜在方法。 作为一种α螺旋介导的PPI，限制关键的组蛋白H3螺旋（残基118-135）是一种策略，通过这种策略，化学探针可能会被精心设计以验证这一假设。在这项工作中，变体H3118- 135肽在theiandi+4位带有戊烯基甘氨酸残基，受到烯烃复分解的限制。生物物理学分析表明，促进生物活性螺旋构象取决于在其中的约束被引入的位置，但对ASF 1的结合的效力是不受约束，而是发生熵补偿。
Inhibiting the histone H3–ASF1 (anti‐silencing function 1) protein–protein interaction (PPI) represents a potential approach for treating numerous cancers. As an α‐helix‐mediated PPI, constraining the key histone H3 helix (residues 118–135) is a strategy through which chemical probes might be elaborated to test this hypothesis. In this work, variant H3118–135peptides bearing pentenylglycine residues at theiandi+4 positions were constrained by olefin metathesis. Biophysical analyses revealed that promotion of a bioactive helical conformation depends on the position at which the constraint is introduced, but that the potency of binding towards ASF1 is unaffected by the constraint and instead that enthalpy–entropy compensation occurs.