As a result of their high specificity for their corresponding biological targets, peptides have shown significant poten-tial in a range of diagnostic and therapeutic applications. However, their widespread use has been limited by their minimal cell permeability and stability in biological milieus. We describe here a hepta-dicyanomethylene-4H-pyran appended β-cyclodextrin (DCM7-β-CD) that acts as a delivery enhancing "host" for 1-bromonaphthalene-modified peptides, as demonstrated with peptide probes P1-P4. Interaction between the fluorescent peptides P1-P3 and DCM7-β-CD results in the hierarchical formation of unique supramolecular architectures, which we term supramo-lecular-peptide-dots (Spds). Each Spd (Spd-1, Spd-2, Spd-3) was found to facilitate the intracellular delivery of the constituent fluorescent probes (P1-P3), thus allowing spatiotemporal imaging of an apoptosis biomarker (caspase-3) and mitosis. Spd-4, incorporating the antimicrobial peptide P4, was found to provide an enhanced therapeutic bene-fit against both gram-positive and gram-negative bacteria relative to P4 alone. In addition, a fluorescent Spd-4 was prepared, which revealed greater bacterial cellular uptake compared to the peptide alone (P4-FITC) in E. coli. (ATCC 25922) and S. aureus (ATCC 25923). This latter observation supports the suggestion that the Spd platform reported here has the ability to facilitate the delivery of a therapeutic peptide and provides an easy-to-implement strategy for enhancing the antimicrobial efficacy of known therapeutic peptides. The present findings thus serve to highlight a new and effective supramolecular delivery approach that is potentially generalizable to overcome limitations associ-ated with functional peptides.

中文翻译：

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增强基于肽的荧光成像和抗菌功效的基于环糊精的肽自组装 (Spds)

由于它们对相应生物靶标的高度特异性，肽在一系列诊断和治疗应用中显示出巨大的潜力。然而，它们的广泛使用受到它们在生物环境中的最小细胞渗透性和稳定性的限制。我们在这里描述了一种七-二氰基亚甲基-4H-吡喃附加 β-环糊精 (DCM7-β-CD)，它作为 1-溴萘修饰肽的递送增强“宿主”，如肽探针 P1-P4 所示。荧光肽 P1-P3 和 DCM7-β-CD 之间的相互作用导致独特的超分子结构的分层形成，我们称之为超分子肽点 (Spds)。发现每个 Spd（Spd-1、Spd-2、Spd-3）促进组成荧光探针（P1-P3）的细胞内递送，因此允许对细胞凋亡生物标志物 (caspase-3) 和有丝分裂进行时空成像。发现结合抗微生物肽 P4 的 Spd-4 相对于单独的 P4 可提供增强的针对革兰氏阳性和革兰氏阴性细菌的治疗益处。此外，还制备了荧光 Spd-4，与大肠杆菌中的单独肽 (P4-FITC) 相比，它显示出更多的细菌细胞吸收。(ATCC 25922) 和金黄色葡萄球菌 (ATCC 25923)。后一种观察结果支持这样的建议，即此处报道的 Spd 平台有能力促进治疗性肽的递送，并提供一种易于实施的策略来增强已知治疗性肽的抗菌功效。