Probing the extraordinary bioactivity of macrocyclic natural products: privileged motifs or biosynthetic artefacts?

化学生物学和药物化学领域需要收集可能具有药物活性的分子。可以筛选这样的集合以鉴定与生物分子如蛋白质相互作用的小分子。这些小分子可以揭示生物过程的基本见解，有时最终可以用于治疗疾病。该基金将探索化学家可以用来设计小分子集合的基本原理。天然存在的小分子，称为天然产物，必然具有生物活性。这些分子中的许多具有大的环状结构。这项资助将探索这种类型的结构是否使小分子倾向于生物活性。一系列类似天然产物的小分子将通过扩展多样性导向的化学来制备，该化学是通过纳尔逊教授的EPSRC高级奖学金开发的。这些分子中的一些将具有大的环状结构，而另一些则没有。将对这些分子进行广泛的生物活性筛选。通过比较各类分子的生物学特征，我们将能够解决大环分子是否从根本上倾向于生物活性的基本化学问题。此外，该补助金将鼓励物理和生命科学之间的博士后流动性，并为EPSRC发出足够的优先权，以发出最近的呼吁。

The fields of Chemical Biology and Medicinal Chemistry require collections of molecules which are likely to be biogically active. Such collections can be screened to identify small molecules which interact with biological molecules such as proteins. Such small molecules can reveal fundamental insights into biological processes and can sometimes be ultimately used to treat diseases.The grant will explore the fundamental principles which chemists can use to design collections of small molecules. Naturally occurring small molecules, known as natural products, are necessarily biologically active. Many of these molecules have large cyclic structures. This grant will explore whether this type of structure predisposes small molecules towards biological activity.A collection of natural product-like small molecules will be prepared by extending diversity-oriented chemistry which has been developed through Professor Nelson's EPSRC Advanced fellowship. Some of these molecules will have large cyclic structures, and others will not. The molecules will be screened for a broad range of biological activities. By comparing the biological profiles of the classes of molecules, we will be able to address the fundamental chemical question of whether macrocyclic molecules are fundamentally predisposed towards biological activity. In addition, the grant will encourage postdoctoral mobility between physical and life sciences, and sufficient priority for EPSRC issued to issue a recent call.