Biomimetic Diversity Oriented Synthesis of Panepophenanthrin-like Molecules.

在高通量生物学的革命时代，新的基因和蛋白质正在迅速涌现。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的靶点的潜力，科学家需要分子工具来探索这些系统。众所周知的和新的化学工具的最好来源之一是自然，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，这些分子往往从天然来源中供应不足，化学家需要从可用的起始材料中合成这些分子。然而，如果此类化合物过于复杂或需要多步合成，则并不总是能够制造足够数量的此类化合物。因此，开发化学合成衍生方法的需求不断增长，这些方法允许快速获得多官能化的、复杂的天然产物类分子。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出现的生物靶标的角色和功能以及验证它们的生物反应方面都是智能的、强大的工具。化学家用来制造天然产物如分子的一种方法被称为仿生合成。仿生的--源自希腊语bios，意思是生命，而模仿--是模仿的形容词--模仿或模仿，是将自然界中发现的方法和系统应用于合成系统的研究和设计。这种技术转移是可取的，因为进化压力通常会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品的方式有时可以促进获得复杂的结构，否则可能需要不可思议的传统合成途径。在这项研究项目中，我们建议使用仿生方法建立一个(许多不同的)复杂的天然产品样结构库。这些分子将使用固相技术制造，这种技术允许通过将化合物附着在可以从反应容器中取出的塑料珠子上来快速提纯化合物。一旦我们制造了许多不同的分子，我们将测试它们与一系列癌细胞的作用，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过程的新工具，甚至可能发现潜在的抗癌新药。

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.