Bató Csaba, Szabó Ildikó, Yousef Mo'ath, Lenzinger Dorina, Grébecz Fülöp Károly, Visnovitz Tamás, Bősze Szilvia E, Bánóczi Zoltán, Mező Gábor
Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, ELTE Eötvös Loránd University, Pázmány Péter Sétány 1/A, 1117 Budapest, Hungary.
Hevesy György PhD School of Chemistry, Institute of Chemistry, ELTE Eötvös Loránd University, Pázmány Péter Sétány 1/A, 1117 Budapest, Hungary.
Int J Mol Sci. 2025 Feb 28;26(5):2202. doi: 10.3390/ijms26052202.
Getting through the cell membrane is challenging, and transporting a therapeutic agent while entering the cell is even more complicated. Cell-penetrating peptides (CPPs) are valuable tools for solving this problem, although they have drawbacks. In this work, the synthesis and investigation of efficient CPPs are described. We used an aromatic group, 1-pyrene carboxylic acid (PCA), to enhance internalization. We designed oligoarginines to investigate the effect of PCA in different positions at the -terminus or in the side chain. Our novel peptide derivatives showed remarkable internalization on tumor cell lines, and more than one endocytic pathway plays a role in their internalization mechanism. With this modification, there is an opportunity to design short oligoarginines that can rival well-known CPPs like octaarginine in internalization.
穿透细胞膜具有挑战性，而在进入细胞的同时运输治疗剂则更为复杂。细胞穿透肽（CPPs）是解决这一问题的有价值工具，尽管它们存在缺点。在这项工作中，描述了高效CPPs的合成与研究。我们使用芳香基团1-芘羧酸（PCA）来增强内化作用。我们设计了寡聚精氨酸来研究PCA在N端不同位置或侧链中的作用。我们的新型肽衍生物在肿瘤细胞系上表现出显著的内化作用，并且不止一种内吞途径在其内化机制中发挥作用。通过这种修饰，有机会设计出在内化作用方面可与八聚精氨酸等知名CPPs相媲美的短寡聚精氨酸。
