Department of Inorganic and Organic Chemistry, ESTCE, University Jaume I , Castellón. Spain.
Acc Chem Res. 2014 Jan 21;47(1):112-24. doi: 10.1021/ar400085p. Epub 2013 Aug 20.
For years researchers have tried to understand the molecular behavior of complex biomolecules through the development of small molecules that can partially mimic their function. Now researchers are implementing the reverse approach: using the structural and mechanistic knowledge obtained from those complex systems to design small molecules with defined properties and for specific applications. One successful strategy for constructing bioinspired, minimalistic molecules is to combine natural building blocks that provide functional elements with abiotic fragments that serve as structural scaffolds. Therefore pseudopeptidic compounds, most of them based on C2 symmetric structures, represent a unique opportunity to explore and evaluate this approach. Some of these molecules are as simple as two amino acids connected by a diamino spacer. The results in this Account show how bioinspired minimalistic pseudopeptides can form ordered structures, participate in the recognition and transcription of information events in molecular devices, and catalyze reactions. This strategy allows researchers to design and prepare a variety of open-chain and macrocyclic compounds leading to systems that can self-aggregate to form hierarchically ordered micro- and nanostructures. In addition, small changes in the molecule or external stimuli can regulate the self-aggregation pattern. In the same way, researchers can also tune the molecular movements of simple pseudopeptides through environmental factors, providing a means to control new molecular devices. In addition, some of the prepared model compounds have shown interesting properties in molecular recognition and even as sensors for several targets of interest. Finally we have observed remarkable catalytic activities from these types of molecules, although those results are still far from the efficiency shown by natural peptides. This family of pseudopeptidic compounds offers the opportunity for the more elaborate design of relatively simple abiotic but bioinspired systems that display specific properties. In addition, the results can provide additional information that will increase the molecular understanding of the basic principles that underlie the extraordinary behavior of natural systems.
多年来，研究人员一直试图通过开发可以部分模拟其功能的小分子来了解复杂生物分子的分子行为。现在，研究人员正在实施相反的方法：利用从这些复杂系统中获得的结构和机制知识来设计具有特定性质和特定应用的小分子。构建受生物启发的简约分子的一种成功策略是将提供功能元素的天然构建块与作为结构支架的非生物片段结合使用。因此，拟肽化合物（大多数基于 C2 对称结构）代表了探索和评估该方法的独特机会。其中一些分子非常简单，例如由二氨基间隔基连接的两个氨基酸。本专题介绍了受生物启发的简约拟肽如何形成有序结构，参与分子器件中信息事件的识别和转录，以及催化反应。该策略允许研究人员设计和制备各种开链和大环化合物，从而导致可以自组装形成分级有序的微纳结构的系统。此外，分子或外部刺激的微小变化可以调节自组装模式。同样，研究人员还可以通过环境因素调节简单拟肽的分子运动，从而提供控制新分子器件的手段。此外，一些制备的模型化合物在分子识别中表现出有趣的性质，甚至作为几种感兴趣的靶标的传感器。最后，我们观察到这些类型的分子具有显著的催化活性，尽管这些结果与天然肽显示的效率相比还有很大的差距。这类拟肽化合物为相对简单的非生物但受生物启发的系统提供了更精细设计的机会，这些系统具有特定的性质。此外，这些结果可以提供额外的信息，从而增加对自然系统非凡行为基础的基本原理的分子理解。
