Biomimetic Diversity Oriented Synthesis of Panepophenanthrin-like Molecules.

在高通量生物学的革命时代，新的基因和蛋白质迅速涌现。为了了解这些基因和蛋白质的生物学相关性和功能，并确定它们作为治疗人类疾病靶点的潜力，科学家们需要分子工具来探测这些系统。众所周知的新化学工具的最佳来源之一是大自然，这些天然产物在帮助解开复杂的生物机制方面发挥了重要作用。不幸的是，这些分子通常缺乏天然来源，化学家需要从可用的起始材料合成这些分子。然而，如果这些化合物太复杂或需要多步合成，就不可能总是制造出足够数量的化合物。因此，开发化学合成衍生方法的需求不断增长，这些方法可以快速获得多功能化、复杂的天然产物样分子。这在很大程度上是因为这些基于小分子的化合物在理解新兴生物靶点的作用和功能以及验证其生物反应方面都是智能，强大的工具。化学家们用来制造天然产物分子的一种方法被称为仿生学合成。仿生学（Biomimetic）来自希腊语单词bios，意思是生命，而mimic是mimesis的形容词，意思是模仿或模仿，是将自然界中发现的方法和系统应用于研究和设计合成系统。这种技术转移是可取的，因为进化压力通常迫使自然系统变得高度优化和高效。因此，模仿大自然制造天然产物的方式有时可以方便地获得复杂的结构，否则可能需要难以想象的传统合成途径。在这个研究项目中，我们建议使用仿生方法制作一个复杂的天然产品样结构库（许多不同的）。这些分子将使用固相技术制造，这种技术可以通过将化合物附着在一个可以从反应容器中取出的塑料头上，从而实现化合物的快速纯化。一旦我们制造出许多不同的分子，我们就会对一系列癌细胞进行测试，以确定它们是否具有生物活性。这可能有助于我们发现研究癌细胞生物学过程的新工具，甚至可能发现潜在的新型抗癌药物。

In the revolutionary age of high-throughput biology, novel genes and proteins are emerging quickly. In order to understand the biological relevance and function of these genes and proteins, and to determine their potential as targets for treating human disease, scientists need molecular tools to probe these systems.One of the best sources of well-known and new chemical tools is Nature, and such natural products have been instrumental in helping unravel complex biological mechanisms. Unfortunately, these molecules are often in short supply from the natural source, and chemists are required to synthesise these molecules from available starting materials. However, it is not always possible to make such compounds in sufficient quantity if they are too complex or require multi-step syntheses.Therefore the need for developing chemical synthesis-derived methods that allow rapid access to poly-functionalised, complex natural product-like molecules is growing constantly. This is largely because these small molecule-based compounds serve as smart, powerful tools both in understanding the roles and functions of emerging biological targets, and in validating their biological responses. One approach that chemists adopt to make natural-product like molecules is termed a biomimetic-synthesis. Biomimetic - from the Greek word bios , meaning life, and mimetic-the adjective for mimesis -- imitation or mimicry, is the application of methods and systems found in nature to the study and design of synthetic systems. This technology transfer is desirable because evolutionary pressure typically forces natural systems to become highly optimised and efficient. Thus, mimicking the way Nature makes natural products can sometimes facilitate access to complex structures that may otherwise require inconceivable conventional synthetic pathways. In this research project, we propose to make a library (many different) of complex natural product-like structures using a biomimetic approach. The molecules will be built using solid-phase techniques, which allow for the rapid purification of compounds by attaching them to a plastic bead that can be picked out of the reaction vessel. Once we have made lots of different molecules, we will test them against a range of cancer cells to determine if they have biological activity. This may help us discover new tools for studying the biological processes of cancer cells, or may even uncover potential new anti-cancer drugs.