Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions.
Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions.
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DOI：
10.1002/anie.201410810
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发表时间：
2015-03-02
期刊：
影响因子：
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通讯作者：
Wilson AJ
中科院分区：
文献类型：
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作者：
Barnard A;Long K;Martin HL;Miles JA;Edwards TA;Tomlinson DC;Macdonald A;Wilson AJ
蛋白质-蛋白质相互作用（PPI）的抑制是化学生物学和药物发现的主要挑战。α-干扰素介导的PPI可能适合使用称为“蛋白质组学”的通用化学型进行调节，其可以以模块化方式组装，以再现PPI内一个配偶体的螺旋基序上发现的关键侧链的载体呈递。在这项工作中，它表明，通过使用一个库的N-烷基化的芳族低聚酰胺螺旋模拟物，有效的螺旋模拟物，再现其生物物理结合的选择性，在细胞的情况下，可以确定。
Inhibition of protein–protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed “proteomimetics”, which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified.