Department of Medicinal Chemistry, Science for Life Laboratory, Uppsala University, Box 574, 75123, Uppsala, Sweden.
Department of Clinical Science, Intervention and Technology (CLINTEC) and Department for Digestive Diseases, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
Angew Chem Int Ed Engl. 2018 Oct 15;57(42):13805-13809. doi: 10.1002/anie.201804828. Epub 2018 Sep 20.
While metabolites derived from gut microbiota metabolism have been linked to disease development in the human host, the chemical tools required for their detailed analysis and the discovery of biomarkers are limited. A unique and multifunctional chemical probe for mass spectrometric analysis, which contains p-nitrocinnamyloxycarbonyl as a new bioorthogonal cleavage site has been designed and synthesized. Coupled to magnetic beads, this chemical probe allows for straightforward extraction of metabolites from human samples and release under mild conditions. This isolation from the sample matrix results in significantly reduced ion suppression, an increased mass spectrometric sensitivity, and facilitates the detection of metabolites in femtomole quantities. The chemoselective probe was applied to the analysis of human fecal samples, resulting in the discovery of four metabolites previously unreported in this sample type and confirmation of the presence of medically relevant gut microbiota-derived metabolites.
虽然源自肠道微生物群代谢的代谢物与人类宿主的疾病发展有关，但用于详细分析和发现生物标志物的化学工具是有限的。我们设计并合成了一种独特的、多功能的用于质谱分析的化学探针，其中包含 p-硝肉桂酰氧基羰基作为新的生物正交裂解位点。该化学探针与磁珠偶联后，可以方便地从人体样本中提取代谢物，并在温和条件下释放。这种从样品基质中的分离显著降低了离子抑制，提高了质谱灵敏度，并有助于检测皮摩尔数量的代谢物。该化学选择性探针应用于人体粪便样本的分析，发现了此前在该样本类型中未报道的四种代谢物，并证实了存在具有医学相关性的肠道微生物群衍生代谢物。
