A nuclear localisation sequence (NLS) peptide, PAAKRVKLD, derived from the human c-Myc regulator gene, has been functionalised with a long wavelength (λ ex = 550 nm; λ em = 677 nm) cyclometalated organometallic iridium(iii) complex to give the conjugate Ir-CMYC. Confocal fluorescence microscopy studies on human fibroblast cells imaged after 18-24 h incubation show that Ir-CMYC concentrations of 80-100 μM promote good cell uptake and nuclear localisation, which was confirmed though co-localisation studies using Hoechst 33342. In comparison, a structurally related, photophysically analogous iridium(iii) complex lacking the peptide sequence, Ir-PYR, showed very different biological behaviour, with no evidence of nuclear, lysosomal or autophagic vesicle localisation and significantly increased toxicity to the cells at concentrations >10 μM that induced mitochondrial dysfunction. Supporting UV-visible and circular dichroism spectroscopic studies show that Ir-PYR and Ir-CMYC display similarly low affinities for DNA (ca. 103 M-1), consistent with electrostatic binding. Therefore the translocation and nuclear uptake properties of Ir-CMYC are attributed to the presence of the PAAKRVKLD nuclear localisation sequence in this complex.

中文翻译：

---

与 c-Myc 信号肽缀合的深红色发光铱 (iii) 复合物的靶向细胞成像特性。

核定位序列 (NLS) 肽 PAAKRVKLD 源自人类 c-Myc 调节基因，已使用长波长（λ ex = 550 nm；λ em = 677 nm）环金属化有机金属铱 (iii) 复合物进行功能化，以产生共轭 Ir-CMYC。对孵育 18-24 小时后成像的人成纤维细胞进行的共聚焦荧光显微镜研究表明，80-100 μM 的 Ir-CMYC 浓度可促进良好的细胞摄取和核定位，这一点通过使用 Hoechst 33342 的共定位研究得到证实。缺乏肽序列的结构相关、光物理类似的铱(iii)复合物，Ir-PYR，表现出非常不同的生物学行为，没有核、溶酶体或自噬囊泡定位的证据，并且在浓度 >10 μM 时对细胞的毒性显着增加，诱导线粒体功能障碍。支持紫外-可见光和圆二色性光谱研究表明，Ir-PYR 和 Ir-CMYC 对 DNA 表现出类似的低亲和力（约 103 M-1），这与静电结合一致。因此，Ir-CMYC 的易位和核摄取特性归因于该复合物中 PAAKRVKLD 核定位序列的存在。