Conformationally rigid proteomimetics: a case study in designing antimicrobial aryl oligomers
Conformationally rigid proteomimetics: a case study in designing antimicrobial aryl oligomers
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DOI：
10.1039/b714490n
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发表时间：
2008-02-07
影响因子：
3.2
通讯作者：
Tew, Gregory N.
中科院分区：
文献类型：
--
作者：
Gabriel, Gregory J.;Tew, Gregory N.
蛋白质组学提供了一个庞大的蛋白质结构数据库，这对希望对蛋白质结构和功能之间的关系有前所未有的了解的科学家来说是令人兴奋的。这些强大的知识将为蛋白质模拟物的设计规则提供深入了解，蛋白质模拟物是低聚物和聚合物，它们比天然蛋白质更稳定，生产成本更低，但仍然模仿天然分子的主要生物学功能。这篇新兴领域的文章旨在激发对设计下一代蛋白质模拟物的创新策略的讨论。具体来说，我们将研究的设计演变的facially两亲性芳基低聚物，化合物，作为合成模拟的抗菌肽（SMAMP），并已知与脂质双层相互作用。抗微生物聚合物领域中日益重要的目标是开发策略以合理地设计膜结合SMAMP，其具有高度细胞选择性，来自任何优选的主链和分子量。预计从研究这些低聚物中获得的经验教训可以应用于其他系统，其中需要模拟物与扩展表面相互作用，并且考虑用大分子模拟感兴趣的蛋白质将是最有效的。明显的例子包括破坏蛋白质-蛋白质相互作用或结合DNA的长片段来控制基因表达。
The promise of proteomics to provide a vast library of protein structural data is exciting to scientists desiring an unprecedented understanding of the relationship between protein structure and function. This powerful knowledge will provide insight into the design rules for proteomimetics which are oligomers and polymers that can be more stable and inexpensive to produce than natural proteins, but still emulate the main biological function of the natural molecule. This Emerging Area article is intended to stimulate discussion on innovative strategies to design the next generation of proteomimetics. Specifically we will examine the design evolution of facially amphiphilic aryl oligomers, compounds that act as synthetic mimics of antimicrobial peptides (SMAMPs) and are known to interact with lipid bilayers. An increasingly important goal in the field of antimicrobial polymers is to develop strategies to rationally design membrane-binding SMAMPs, that are highly cell-selective, from any preferred backbone and molecular weight. It is expected that lessons learned from studying these oligomers can be applied to other systems where mimics are desired to interact with extended surfaces and where it would be most productive to consider mimicking the protein of interest with a large molecule. Obvious examples include disrupting protein-protein interactions or binding long tracts of DNA to control gene expression.