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1-Pyrene Carboxylic Acid: An Internalization Enhancer for Short Oligoarginines

Bató, Csaba and Szabó, Ildikó and Yousef, Mo’ath and Lenzinger, Dorina and Grébecz, Fülöp Károly and Visnovitz, Tamás and Bősze, Szilvia and Bánóczi, Zoltán and Mező, Gábor (2025) 1-Pyrene Carboxylic Acid: An Internalization Enhancer for Short Oligoarginines. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 26 (5). No. 2202. ISSN 1661-6596

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Abstract

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 N-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.

Item Type: Article
Additional Information: Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, ELTE Eötvös Loránd University, Pázmány Péter Sétány 1/A, Budapest, 1117, Hungary Hevesy György PhD School of Chemistry, Institute of Chemistry, ELTE Eötvös Loránd University, Pázmány Péter Sétány 1/A, Budapest, 1117, Hungary HUN-REN-ELTE Research Group of Peptide Chemistry, Budapest, 1117, Hungary MTA-TTK Lendület “Momentum” Peptide-Based Vaccines Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest, 1117, Hungary Ecole Super Biotechnol Strasbourg ESBS, CNRS, UMR 7242, Biotechnol & Cellular Signalling, University Strasbourg, Illkirch Graffenstaden, F-67400, France Department of Genetics, Cell- and Immunobiology, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary Department of Plant Physiology and Molecular Plant Biology, ELTE Eötvös Loránd University, Pázmány Péter Sétány 1/c, Budapest, 1117, Hungary Export Date: 28 March 2025; Cited By: 0; Correspondence Address: Z. Bánóczi; Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, ELTE Eötvös Loránd University, Budapest, Pázmány Péter Sétány 1/A, 1117, Hungary; email: zoltan.banoczi@ttk.elte.hu; G. Mező; Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, ELTE Eötvös Loránd University, Budapest, Pázmány Péter Sétány 1/A, 1117, Hungary; email: gabor.mezo@ttk.elte.hu
Uncontrolled Keywords: cell-penetrating peptide; aromatic modification; transport molecule; hydrophobic molecule
Subjects: Q Science / természettudomány > QD Chemistry / kémia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 15 Sep 2025 12:38
Last Modified: 15 Sep 2025 12:38
URI: https://real.mtak.hu/id/eprint/224269

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