Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
PLoS One. 2013 Aug 9;8(8):e71752. doi: 10.1371/journal.pone.0071752. eCollection 2013.
Cell-penetrating peptides (CPPs) are a promising tool to overcome cell membrane barriers. They have already been successfully applied as carriers for several problematic cargoes, like e.g. plasmid DNA and (si)RNA, opening doors for new therapeutics. Although several hundreds of CPPs are already described in the literature, only a few commercial applications of CPPs are currently available. Cellular uptake studies of these peptides suffer from inconsistencies in used techniques and other experimental conditions, leading to uncertainties about their uptake mechanisms and structural properties. To clarify the structural characteristics influencing the cell-penetrating properties of peptides, the chemical-functional space of peptides, already investigated for cellular uptake, was explored. For 186 peptides, a new cell-penetrating (CP)-response was proposed, based upon the scattered quantitative results for cellular influx available in the literature. Principal component analysis (PCA) and a quantitative structure-property relationship study (QSPR), using chemo-molecular descriptors and our newly defined CP-response, learned that besides typical well-known properties of CPPs, i.e. positive charge and amphipathicity, the shape, structure complexity and the 3D-pattern of constituting atoms influence the cellular uptake capacity of peptides.
细胞穿透肽（CPPs）是一种有前途的克服细胞膜屏障的工具。它们已经成功地被用作几种有问题的货物的载体，例如质粒 DNA 和（si）RNA，为新的治疗方法开辟了道路。尽管文献中已经描述了数百种 CPP，但目前只有少数 CPP 的商业应用。这些肽的细胞摄取研究受到所用技术和其他实验条件的不一致性的影响，导致对其摄取机制和结构特性存在不确定性。为了阐明影响肽细胞穿透特性的结构特征，研究人员探索了已经研究过细胞摄取的肽的化学功能空间。基于文献中可获得的细胞内流的分散定量结果，针对 186 种肽提出了新的细胞穿透（CP）反应。主成分分析（PCA）和使用化学分子描述符和我们新定义的 CP 反应的定量结构-性质关系研究（QSPR）表明，除了 CPP 的典型特征，即正电荷和两亲性外，肽的形状、结构复杂性和构成原子的 3D 模式也会影响其细胞摄取能力。
