Medicinal Chemistry Core

药物化学核心（MCC; Core D）将提供化学资源，以补充各自项目团队中的现有资源。MCC的资源将凭借其丰富的药物化学经验与抗菌药物的学术基础而脱颖而出。至关重要的是，世纪挑战集团的工作人员已经在制药行业展示了他们通过进化小分子来发现候选药物的能力，以解决在此过程中遇到的广泛问题。这一经验将对以下项目至关重要：项目1)芳丙基三烷基间苯三酚家族小分子抗菌药物的优化。项目2)结核分枝杆菌必需代谢酶（如Pks13）的小分子抑制剂的进化。项目4)非核糖体编码肽的固相合成，具有重要的抗菌潜力；项目5)利用贝叶斯计算模型发现和优化小分子抗菌药物。这些项目需要在每个MCC成员的背景描述中找到的各种化学方面的经验。总体而言，MCC员工化学背景的广度和深度将证明他们将个人项目中的基础科学发现转化为具有积极影响抗菌临床前景以应对全球健康危机的小分子的巨大潜力的能力至关重要。

The Medicinal Chemistry Core (MCC; Core D) will provide chemistry resources complementary to those existing within the respective project teams. The MCC resource will distinguish itself by relying on extensive pharmaceutical medicinal chemistry experience melded with an academic foundation in antibacterials. Critically, the MCC staff have demonstrated in the pharmaceutical industry setting their ability to discover drug candidates by evolving small molecules to address a wide range of problems encountered during the process. This experience will be essential to: Project 1) the optimization of small molecules ofthe arylpropionyl trialkylphloroglucinol family as antibacterials. Project 2) the evolution of small molecule inhibitors of essential metabolic enzymes, such Pks13, in M. tuberculosis. Project 4) the solid-phase synthesis of non-ribosomally encoded peptides with significant potential as antibacterials, and Project 5) the discovery and optimization of small molecule antibacterials leveraging Bayesian computational models. These projects necessitate experience with a diverse range of chemistries as found in the description of each MCC member's background. Overall, the spectrum and depth ofthe MCC staffs chemistry background will prove critical to their ability to translate basic scientific discoveries within the individual projects to small molecules with significant potential for positively impacting the antibacterial clinical landscape to address the global health crisis.