Specific labeling with potent radiolabels alters the uptake of cell‐penetrating peptides
Specific labeling with potent radiolabels alters the uptake of cell‐penetrating peptides
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强效放射性标记的特异性标记改变了细胞穿透肽的摄取
作者：
C. Walther;I. Ott;R. Gust;I. Neundorf
放射性标记肽不仅作为肿瘤标记物，而且作为转运载体，在放射药物学中发挥着重要作用。因此，细胞穿透肽（CPP）也可以作为非常有效的递送工具。最近，已经开发了基于人激素降钙素（hCT）的CPP。特别是，分支hCT肽序列被证明具有高效的内化能力。用放射性核素标记这些肽将产生用于放射性药物学中的成像和治疗应用的有前途的新工具。然而，金属络合对CPP内化能力的影响尚未得到详细阐明。在这项研究中，我们通过使用原子吸收光谱法（AAS）定量HeLa细胞中Ga-DOTA修饰的hCT-载体肽的摄取，并将结果与荧光标记肽的摄取进行比较。有趣的是，我们测量了不同的吸收率，这取决于所附的标签。出乎意料的是，用Ga-DOTA络合物修饰可以对吸收效率具有巨大的影响。这些研究的结果支持需要详细分析每个载体肽/货物构建体，特别是在金属络合物修饰的CPP领域。© 2009 Wiley Periodicals，Inc. Biopolymers（Pept Sci）92：445-451，2009.
Radiolabeled peptides play an important role in radiopharmacy not only as tumor markers but also as transport vectors. Therefore, cell‐penetrating peptides (CPP) may serve as very effective delivery tools, as well. Recently, CPP based on the human hormone calcitonin (hCT) have been developed. Especially, branched hCT‐peptide sequences turned out to have highly efficient internalization capacities. Labeling these peptides with radionuclides would generate promising new tools for imaging and therapy applications in radiopharmacy. However, the influence of the metal complexation on the internalization capacity of CPP has not been elucidated yet in detail. In this study we quantified the uptake of Ga‐DOTA modified hCT‐carrier peptides in HeLa cells by using atomic absorption spectroscopy (AAS) and compared the results to the uptake of fluorescently‐labeled peptides. Interestingly, we measured different uptake rates depending on the attached label. Unexpectedly, modification with a Ga‐DOTA complex can have tremendous effects on the uptake efficiency. The results of these studies support the need of detailed analysis of each carrier peptide/cargo construct, especially in the field of metal complex modified CPP. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 445–451, 2009.