HRAM (High Resolution Accurate Mass)-Liquid Chromatography Hybrid Mass Spectrometer

活性药物成分、药物代谢物、候选药物的合成和分析，以及部分以复杂基质形式的生物合成途径、细菌多糖降解机理和天然物质的结构澄清的研究，是格雷夫斯瓦尔德大学药学研究所参与工作组的研究工作重点。所有上述问题都需要高分辨率准确的质量测量数据，这些数据以前可以使用研究所运行的混合质谱仪系统来收集。该系统在使用13年后不再运行，将在平等的基础上进行更换。由于性能显著提高的液相色谱系统(超高性能液相色谱)已经变得越来越成熟，因此这一次将获得这样的混合系统。使用所要求的设备确定分析物准确质量的能力得到内部两个单四极系统和三个四极质谱计的补充，该质谱仪于2020年购买，用于灵敏的定量，使用该仪器无法以必要的精度测量高分辨率的准确质量数据。此外，该研究所还研究药物在生物体和模型系统中的传输、药物形式中活性成分的释放以及人类病原菌的耐药机制和毒力因素，这些问题迄今尚未使用高分辨率准确的质量数据，但可以通过精确的质量测量获得更多的见解。所要求的设备配置旨在保持和丰富整个药物研究所的研究机会。研究目标是澄清钾通道调节剂作用和副作用的分子和超分子基础、sirtuin抑制剂、药物代谢物的鉴定和定量、人工酶产品混合物的研究和制备性纯化、双肽和三肽转运体的“转运体”的特征、非洲药用植物提取物成分的结构特征、发现新的原天冬氨酸酶-3激活剂的合成产品的特征、人类免疫细胞中未知的脂质介体和白色念珠菌的新氧脂、共生海洋生物的蛋白质组学以及细菌多糖降解的未知机制。

The synthesis and analysis of active pharmaceutical ingredients, drug metabolites, drug candidates as well as the investigation of biosynthesis pathways, mechanisms of bacterial polysaccharide degradation and structural clarification of natural substances, partly in complex matrices, are the focus of the research work of the participating working groups of the Institute of Pharmacy at the University of Greifswald. High resolution accurate mass measurement data are required for all of the above questions, which could previously be collected using a hybrid mass spectrometer system operated in the institute. The system, which is no longer operational after 13 years of use, is to be replaced on an equal footing. Since liquid chromatography systems with significantly increased performance (ultra high performance liquid chromatography) have become increasingly established, a such a hybrid system is to be procured this time. The ability to determine the exact mass of analytes with the requested device is complemented by the in-house two single-quadrupole systems and the triple quadrupole mass spectrometer, which was purchased in 2020 for sensitive quantification and with which no high resolution accurate mass data can be measured with the necessary accuracy.The above-mentioned works are supplemented on the one hand by cellular assays for the study of biological activity and pathophysiological stimuli as well as other proteomics projects in the field of marine biotechnology. In addition, the institute deals with questions about the transport of drugs in the organism and in model systems, the release of active ingredients from drug forms and resistance mechanisms and virulence factors of human pathogenic bacteria, for which no high resolution accurate mass data has been used so far, but for which additional insights could be gained by exact mass measurements. The requested device configuration is intended to maintain and enrich the research opportunities of the entire Institute of Pharmacy.Research objectives are to clarify the molecular and supramolecular basis of the effects and side effects of potassium channel modulators, identification and quantification of sirtuin inhibitors, drug metabolites and investigation and preparative purification of product mixtures of artificial enzymes, characterization of the "transportophore" of di- and tripeptide transporters, structural characterization of components from African medicinal plant extracts, characterization of synthesis products for the discovery of new procaspase-3 activators, identification of unknown lipid mediators in human immune cells and new oxylipins from Candida albicans, proteogenomics of symbiotic marine organisms and clarification of unknown mechanisms of bacterial polysaccharide degradation.