Peptide-based inhibitors of protein-protein interactions: biophysical, structural and cellular consequences of introducing a constraint.
Peptide-based inhibitors of protein-protein interactions: biophysical, structural and cellular consequences of introducing a constraint.
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基于肽的蛋白质-蛋白质相互作用抑制剂：引入约束的生物物理、结构和细胞后果。
DOI：
10.1039/d1sc00165e
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发表时间：
2021-03-25
期刊：
影响因子：
8.4
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wang H;Dawber RS;Zhang P;Walko M;Wilson AJ;Wang X
Protein–protein interactions (PPIs) are implicated in the majority of cellular processes by enabling and regulating the function of individual proteins. Thus, PPIs represent high-value, but challenging targets for therapeutic intervention. The development of constrained peptides represents an emerging strategy to generate peptide-based PPI inhibitors, typically mediated by α-helices. The approach can confer significant benefits including enhanced affinity, stability and cellular penetration and is ingrained in the premise that pre-organization simultaneously pays the entropic cost of binding, prevents a peptide from adopting a protease compliant β-strand conformation and shields the hydrophilic amides from the hydrophobic membrane. This conceptual blueprint for the empirical design of peptide-based PPI inhibitors is an exciting and potentially lucrative way to effect successful PPI inhibitor drug-discovery. However, a plethora of more subtle effects may arise from the introduction of a constraint that include changes to binding dynamics, the mode of recognition and molecular properties. In this review, we summarise the influence of inserting constraints on biophysical, conformational, structural and cellular behaviour across a range of constraining chemistries and targets, to highlight the tremendous success that has been achieved with constrained peptides alongside emerging design opportunities and challenges. This review summarizes the influence of inserting constraints on biophysical, conformational, structural and cellular behaviour for peptides targeting α-helix mediated protein–protein interactions.
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影响因子：
6.8
作者：
Rezaei Araghi R;Keating AE
通讯作者：
Keating AE
低氧诱导因子（HIF）是研究抑制蛋白质蛋白质相互作用的模型。
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Edwards AL;Wachter F;Lammert M;Huhn AJ;Luccarelli J;Bird GH;Walensky LD
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Walensky LD
DOI：
10.1073/pnas.1303002110
发表时间：
2013-09-03
影响因子：
11.1
作者：
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通讯作者：
Sawyer, Tomi K.
影响因子：
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Arkin MR;Tang Y;Wells JA
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