This report describes the first synthesis and application of a fluorescent teixobactin analogue that exhibits antibiotic activity and binds to the cell walls of Gram-positive bacteria. The teixobactin analogue, Lys(Rhod)9,Arg10-teixobactin, has a fluorescent tag at position 9 and an arginine in place of the natural allo-enduracididine residue at position 10. The fluorescent teixobactin analogue retains partial antibiotic activity, with minimum inhibitory concentrations of 4-8 μg/mL across a panel of Gram-positive bacteria, as compared to 1-4 μg/mL for the unlabeled Arg10-teixobactin analogue. Lys(Rhod)9,Arg10-teixobactin is prepared by a regioselective labeling strategy that labels Lys9 with an amine-reactive rhodamine fluorophore during solid-phase peptide synthesis, with the resulting conjugate tolerating subsequent solid-phase peptide synthesis reactions. Treatment of Gram-positive bacteria with Lys(Rhod)9,Arg10-teixobactin results in septal and lateral staining, which is consistent with an antibiotic targeting cell wall precursors. Concurrent treatment of Lys(Rhod)9,Arg10-teixobactin and BODIPY FL vancomycin results in septal colocalization, providing further evidence that Lys(Rhod)9,Arg10-teixobactin binds to cell wall precursors. Controls with either Gram-negative bacteria, or an inactive fluorescent homologue with Gram-positive bacteria, showed little or no staining in fluorescence micrographic studies. Lys(Rhod)9,Arg10-teixobactin can thus serve as a functional probe to study Gram-positive bacteria and their interactions with teixobactin.

中文翻译：

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荧光Teixobactin类似物。

该报告描述了具有抗生素活性并结合革兰氏阳性细菌细胞壁的荧光替ixobactin类似物的首次合成和应用。teixobactin类似物Lys（Rhod）9，Arg10-teixobactin在位置9具有荧光标记，在位置10具有精氨酸代替天然的异种内酰胺基残基。该荧光teixobactin类似物保留了部分抗生素活性，具有最小的抑制浓度一组革兰氏阳性细菌的血样浓度为4-8μg/ mL，而未标记的Arg10-teixobactin类似物为1-4μg/ mL。Lys（Rhod）9，Arg10-teixobactin通过区域选择性标记策略制备，该策略在固相肽合成过程中用胺反应性若丹明荧光团标记Lys9，所得的缀合物耐受随后的固相肽合成反应。用Lys（Rhod）9，Arg10-teixobactin处理革兰氏阳性细菌会导致间隔和侧面染色，这与靶向抗生素的细胞壁前体一致。Lys（Rhod）9，Arg10-teixobactin和BODIPY FL万古霉素的同时治疗导致间隔共定位，提供进一步的证据表明Lys（Rhod）9，Arg10-teixobactin与细胞壁前体结合。革兰氏阴性细菌的对照或革兰氏阳性细菌的无活性荧光同源物在荧光显微照片研究中显示很少或没有染色。因此，Lys（Rhod）9，Arg10-teixobactin可以用作研究革兰氏阳性细菌及其与teixobactin相互作用的功能探针。Arg10-teixobactin导致间隔和侧面染色，这与靶向抗生素的细胞壁前体一致。Lys（Rhod）9，Arg10-teixobactin和BODIPY FL万古霉素的同时治疗导致间隔共定位，提供进一步的证据表明Lys（Rhod）9，Arg10-teixobactin与细胞壁前体结合。革兰氏阴性细菌的对照或革兰氏阳性细菌的无活性荧光同源物在荧光显微照片研究中显示很少或没有染色。因此，Lys（Rhod）9，Arg10-teixobactin可以用作研究革兰氏阳性细菌及其与teixobactin相互作用的功能探针。Arg10-teixobactin导致间隔和侧面染色，这与靶向抗生素的细胞壁前体一致。Lys（Rhod）9，Arg10-teixobactin和BODIPY FL万古霉素的同时治疗导致间隔共定位，提供进一步的证据表明Lys（Rhod）9，Arg10-teixobactin与细胞壁前体结合。革兰氏阴性细菌的对照或革兰氏阳性细菌的无活性荧光同源物在荧光显微照片研究中显示很少或没有染色。因此，Lys（Rhod）9，Arg10-teixobactin可以用作研究革兰氏阳性细菌及其与teixobactin相互作用的功能探针。Arg10-teixobactin和BODIPY FL万古霉素导致间隔共定位，进一步提供了Lys（Rhod）9，Arg10-teixobactin与细胞壁前体结合的证据。革兰氏阴性细菌的对照或革兰氏阳性细菌的无活性荧光同源物在荧光显微照片研究中显示很少或没有染色。因此，Lys（Rhod）9，Arg10-teixobactin可以用作研究革兰氏阳性细菌及其与teixobactin相互作用的功能探针。Arg10-teixobactin和BODIPY FL万古霉素导致间隔共定位，进一步提供了Lys（Rhod）9，Arg10-teixobactin与细胞壁前体结合的证据。革兰氏阴性细菌的对照或革兰氏阳性细菌的无活性荧光同源物在荧光显微照片研究中显示很少或没有染色。因此，Lys（Rhod）9，Arg10-teixobactin可以用作研究革兰氏阳性细菌及其与teixobactin相互作用的功能探针。