Department of Chemical Biology, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), Inhoffenstrasse 7, 38124, Braunschweig, Germany.
State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, 100050, P.R. China.
Angew Chem Int Ed Engl. 2017 Jul 3;56(28):8272-8276. doi: 10.1002/anie.201701358. Epub 2017 Jun 13.
There is a strong need to better diagnose infections at deep body sites through noninvasive molecular imaging methods. Herein, we describe the synthesis and characterization of probes based on siderophore conjugates with catechol moieties and a central DOTAM scaffold. The probes can accommodate a metal ion as well as an antibiotic moiety and are therefore suited for theranostic purposes. The translocation of the conjugates across the outer and inner cell membranes of E. coli was confirmed by growth recovery experiments with enterobactin-deficient strains, by the antibacterial activity of ampicillin conjugates, and by confocal imaging using a fluorogen-activating protein-malachite green system adapted to E. coli. The suitability of the probes for in vivo imaging was demonstrated with a Cy5.5 conjugate in mice infected with P. aeruginosa.
非常有必要通过非侵入性的分子成像方法来更好地诊断深部感染。在此，我们描述了基于具有儿茶酚部分和中心 DOTAM 支架的铁载体缀合物的探针的合成和表征。这些探针可以容纳金属离子和抗生素部分，因此适用于治疗诊断目的。通过用缺乏肠菌素的菌株进行生长恢复实验、氨苄青霉素缀合物的抗菌活性以及使用适应于大肠杆菌的荧光团激活蛋白-孔雀石绿系统进行共聚焦成像，证实了这些缀合物穿过大肠杆菌的外膜和内膜的转运。用 Cy5.5 缀合物在感染铜绿假单胞菌的小鼠中进行了体内成像实验，证明了这些探针的适用性。
