As pharmacokinetic modifiers, cell penetrating peptides (CPPs) have proven utility for the delivery of otherwise impermeable cargoes into the discrete intracellular compartments of eukaryotic cells. Methods for the molecular optimisation of CPP sequences can significantly increase the performance of novel vectors matched to a specific delivery function. Moreover, the ‘information rich’ composition and inherent molecular flexibility of many CPPs can also facilitate their interaction with intracellular proteins and other cellular structures. This proteomimetic property of CPPs has been exploited in the design of bioportides, bioactive CPPs that regulate cellular functions often by binding relatively flat PPI interfaces to achieve a dominant negative action. This new biology of CPPs is rapidly gathering momentum through the design and synthesis of a bewildering variety of peptides that may be, in whole or part, linear, helical, cyclic and/or chimeric in nature. A particular emphasis of contemporary CPP‐centred drug discovery is the unmet medical need of cancer, though the biomedical scope of bioportide applications is impressively broad including cellular signalling and reprogramming. We are hopeful that one or more of the fascinating studies described herein will translate into the clinic to establish bioportide technologies as a viable option for drug discovery.

中文翻译：

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细胞穿透肽的新生物学

作为药物代谢动力学的修饰剂，细胞穿透肽（CPPs）已被证明可用于将原本不可渗透的货物递送到真核细胞的离散细胞内区室中。CPP序列分子优化的方法可以显着提高与特定递送功能匹配的新型载体的性能。此外，许多CPP的“信息丰富”组成和固有的分子柔性也可以促进它们与细胞内蛋白质和其他细胞结构的相互作用。CPP的这种蛋白质模拟性质已被用于生物部分的设计中，即具有生物活性的CPP，该CPP通常通过结合相对平坦的PPI界面来调节显性负作用来调节细胞功能。CPP的这种新生物学正在通过设计和合成令人迷惑的各种肽迅速集聚动量，这些肽在本质上可能全部或部分是线性，螺旋，环状和/或嵌合的。尽管以生物疗法为主的生物医学应用范围非常广泛，包括细胞信号转导和重编程，但当代以CPP为中心的药物发现特别强调了对癌症的医疗需求未得到满足。我们希望，本文所述的一项或多项引人入胜的研究将转化为临床，以建立生物载体技术作为药物发现的可行选择。尽管bioportide应用的生物医学范围令人印象深刻，包括细胞信号传导和重编程。我们希望，本文所述的一项或多项引人入胜的研究将转化为临床，以建立生物载体技术作为药物发现的可行选择。尽管bioportide应用的生物医学范围令人印象深刻，包括细胞信号传导和重编程。我们希望，本文所述的一项或多项引人入胜的研究将转化为临床，以建立生物载体技术作为药物发现的可行选择。