Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, United States.
Mol Pharm. 2024 Oct 7;21(10):5255-5260. doi: 10.1021/acs.molpharmaceut.4c00688. Epub 2024 Sep 2.
Intracellular delivery of biological cargos, which would yield new research tools and novel therapeutics, remains an active area of research. A convenient and potentially general approach involves the conjugation of a cell-penetrating peptide to a cargo of interest. However, linear CPPs lack sufficient cytosolic entry efficiency and metabolic stability, while previous backbone cyclized CPPs have several drawbacks including the necessity for chemical synthesis and posttranslational conjugation to peptide/protein cargos and epimerization during cyclization. We report here a new class of bismuth cyclized CPPs with excellent cytosolic entry efficiencies, proteolytic stability, and potential compatibility with genetic encoding and recombinant production.
细胞内生物载体的输送，这将产生新的研究工具和新的治疗方法，仍然是一个活跃的研究领域。一种方便且具有潜在通用性的方法涉及将细胞穿透肽与感兴趣的载体相连接。然而，线性 CPP 缺乏足够的细胞质内进入效率和代谢稳定性，而以前的骨架环化 CPP 存在几个缺点，包括需要化学合成和翻译后修饰以连接到肽/蛋白质载体，以及环化过程中的差向异构化。我们在这里报告了一类新的双环化 CPP，具有优异的细胞质内进入效率、蛋白水解稳定性，并且可能与遗传编码和重组生产兼容。
