Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA.
Theranostics. 2013 Aug 10;3(9):658-66. doi: 10.7150/thno.6811. eCollection 2013.
This study reports the first set of synthetic molecules that act as broad spectrum agglutination agents and thus are complementary to the specific targeting of antibodies. The molecules have dendritic architecture and contain multiple copies of zinc(II)-dipicolylamine (ZnDPA) units that have selective affinity for the bacterial cell envelope. A series of molecular structures were evaluated, with the number of appended ZnDPA units ranging from four to thirty-two. Agglutination assays showed that the multivalent probes rapidly cross-linked ten different strains of bacteria, regardless of Gram-type and cell morphology. Fluorescence microscopy studies using probes with four ZnDPA units indicated a high selectivity for bacteria agglutination in the presence of mammalian cells and no measurable effect on the health of the cells. The high bacterial selectivity was confirmed by conducting in vivo optical imaging studies of a mouse leg infection model. The results suggest that multivalent ZnDPA molecular probes with dendritic structures have great promise as selective, broad spectrum bacterial agglutination agents for infection imaging and theranostic applications.
本研究报告了第一组作为广谱凝集剂起作用的合成分子,因此与抗体的特异性靶向互补。这些分子具有支化结构,包含多个锌(II)-二吡啶甲胺 (ZnDPA) 单元,对细菌细胞包膜具有选择性亲和力。评估了一系列分子结构,其中附加的 ZnDPA 单元数量从四个到三十二个不等。凝集实验表明,多价探针可快速交联十种不同的细菌菌株,而与革兰氏类型和细胞形态无关。使用具有四个 ZnDPA 单元的探针进行荧光显微镜研究表明,在存在哺乳动物细胞的情况下,探针对细菌的凝集具有高选择性,并且对细胞的健康没有可测量的影响。通过对小鼠腿部感染模型进行体内光学成像研究,证实了高细菌选择性。结果表明,具有支化结构的多价 ZnDPA 分子探针具有作为选择性、广谱细菌凝集剂的巨大潜力,可用于感染成像和治疗应用。