Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China.
Chemistry. 2012 Apr 2;18(14):4225-33. doi: 10.1002/chem.201103516. Epub 2012 Feb 29.
A novel zinc(II) phthalocyanine conjugated with a short peptide with a nuclear localization sequence, Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val, was synthesized by click chemistry and a standard Fmoc solid-phase peptide synthesis protocol. The conjugate was purified by HPLC and characterized with UV/Vis and high-resolution mass spectroscopic methods. Both this compound and its non-peptide-conjugated analogue are essentially non-aggregated in N,N-dimethylformamide and can generate singlet oxygen effectively with quantum yields (Φ(Δ)) of 0.84 and 0.81, respectively, relative to unsubstituted zinc(II) phthalocyanine (Φ(Δ) =0.56). Conjugation of the peptide sequence, however, can enhance the cellular uptake, efficiency in generating intracellular reactive oxygen species, and photocytotoxicity of the phthalocyanine-based photosensitizer against HT29 human colorectal carcinoma cells. The IC(50) value of the conjugate is as low as 0.21 μM. In addition, the conjugate shows an enhanced tumor-retention property in tumor-bearing nude mice. After 72 h post-injection, the dye concentration in the tumor was significantly higher than that in other organs. The results suggest that this phthalocyanine-peptide conjugate is a highly promising photosensitizer for photodynamic therapy.
一种新型锌(II)酞菁与具有核定位序列 Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val 的短肽通过点击化学和标准 Fmoc 固相肽合成方案合成。该缀合物通过 HPLC 进行纯化，并通过紫外/可见和高分辨率质谱方法进行表征。该化合物及其非肽缀合类似物在 N,N-二甲基甲酰胺中均基本不聚集，并且可以有效地产生单线态氧，量子产率（Φ(Δ)）分别为 0.84 和 0.81，相对于未取代的锌(II)酞菁（Φ(Δ)=0.56）。然而，肽序列的缀合可以增强基于酞菁的光敏剂对 HT29 人结肠直肠癌细胞的细胞摄取、生成细胞内活性氧的效率和光细胞毒性。该缀合物的 IC(50)值低至 0.21 μM。此外，该缀合物在荷瘤裸鼠中显示出增强的肿瘤保留特性。注射后 72 h，肿瘤中的染料浓度明显高于其他器官。结果表明，这种酞菁-肽缀合物是一种很有前途的光动力治疗光敏剂。
