Synthesis of small molecules for inhition of chlamydial growth

合成用于启动衣原体生长的小分子

• 批准号: 346427390
• 负责人: Professor Dr. Christoph Arenz
• 金额: --
• 依托单位: Arbeitsgruppe Organische und Bioorganische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/346427390?language=en
• 关键词: Synthesis; small; molecules; inhition; chlamydial

We have developed ceramide derivatives with potent anti-chlamydial activity. Potency, structure, in vitro assays and preliminary comparative studies between different chlamydial strains with known anti-chlamydial compounds suggest that these molecules have a novel not yet described mechanism of action. Our preliminary SAR, based on about 30 different compounds however indicates that most likely sphingolipid-specific biomolecules are targeted that could be important components of the chlamydial sphingolipid-acquisition machinery. Our objective is to further develop collections of molecules and to test their effect on the chlamydial life cycle. Chemical synthesis and various bioassays will be applied to identify potent effectors. We will synthesize variants of these effectors that will enable us to crosslink, pull down and identify potential molecular target molecules. Probes are envisioned allowing for dissecting molecular conversion and trafficking of individual lipids within infected cells. An additional important goal is to identify potential pharmaceutical targets and to establish in vitro assays that allow for rapid development of novel antichlamydial compounds. If host biomolecules are targeted by the compounds, it is well possible that these targets could also be interesting to be investigated with regard to other intracellular pathogens. The proposal covers chemical synthesis and bioorganic assay development on the one hand and cell- and infection biology on the other hand.

我们已经开发出具有强效抗衣原体活性的神经酰胺衍生物。效力，结构，在体外试验和不同的衣原体菌株与已知的抗衣原体化合物之间的初步比较研究表明，这些分子有一个新的尚未描述的作用机制。然而，我们基于约30种不同化合物的初步SAR表明，最有可能的鞘脂特异性生物分子是衣原体鞘脂获取机制的重要组成部分。我们的目标是进一步开发分子的集合，并测试它们对衣原体生命周期的影响。将应用化学合成和各种生物测定来鉴定有效的效应物。我们将合成这些效应物的变体，使我们能够交联，下拉和识别潜在的分子靶分子。设想探针允许在感染细胞内解剖分子转化和单个脂质的运输。另一个重要的目标是确定潜在的药物靶点，并建立体外试验，允许快速开发新的抗衣原体化合物。如果宿主生物分子被化合物靶向，则很可能这些靶点也可能是关于其他细胞内病原体的有趣的研究。该提案一方面涵盖化学合成和生物有机分析开发，另一方面涵盖细胞和感染生物学。