A novel cell-penetrating peptide derived from human eosinophil cationic protein
Authors: Lih-Yuan Lin
Tan-chi Fan
Ta-Jen Hung
Chi-Shin Hwang
Shun-lung Fang
Chien-Jung Chen
Margaret Dah-Tsyr Chang
Hua-Wen Fu
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Cell-penetrating peptides; ECP(32-41); internalization; targeting; cysteine
Affiliations: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.

Abstract:  Cell-penetrating peptides (CPPs) are short peptides which can carry various types of molecules into cells; however, although most CPPs rapidly penetrate cells in vitro, their in vivo tissue-targeting specificities are low. Herein, we describe cell-binding, internalization, and targeting characteristics of a newly identified 10-residue CPP, denoted ECP(32-41), derived from the core heparin-binding motif of human eosinophil cationic protein (ECP). Besides traditional emphasis on positively charged residues, the presence of cysteine and tryptophan residues was demonstrated to be essential for internalization. ECP(32-41) entered Beas-2B and wild-type CHO-K1 cells, but not CHO cells lacking of cell-surface glycosaminoglycans (GAGs), indicating that binding of ECP(32-41) to cell-surface GAGs was required for internalization. When cells were cultured with GAGs or pre-treated with GAG-digesting enzymes, significant decreases in ECP(32-41) internalization were observed, suggesting that cell-surface GAGs, especially heparan sulfate proteoglycans were necessary for ECP(32-41) attachment and penetration. Furthermore, treatment with pharmacological agents identified two forms of energy-dependent endocytosis, lipid-raft endocytosis and macropinocytosis, as the major ECP(32-41) internalization routes. ECP(32-41) was demonstrated to transport various cargoes including fluorescent chemical, fluorescent protein, and peptidomimetic drug into cultured Beas-2B cells in vitro, and targeted broncho-epithelial and intestinal villi tissues in vivo. Hence this CPP has the potential to serve as a novel vehicle for intracellular delivery of biomolecules or medicines, especially for the treatment of pulmonary or gastrointestinal diseases. 

Retracted: No

PubPeer comments:
 This is one of a large number of coordination-chemistry papers that appear to have all been written according to a template. - Most draw on two papers by Y. Feng et al. and one by C.-W. Duan et al to illustrate the broad range of applications and properties of MOFs. Notably, these are not papers about MOFs. - - Y. Feng, H. Fan, Z. Zhong, H. Wang, D. Qiu, Inorg. Chem. 2016, 55, 11987u201311992.  Cd3(MoO4)(TeO3)2: A Polar 3D Compound Containing d10-d0 SCALP-Effect Cations - - Y. Feng, M. Li, H. Fan, Q. Huang, D. Qiu, H. Shi, Dalton Trans. 2015, 44, 894u2013897.  A Novel Open-Framework Copper Borophosphate Containing 1-D Borophosphate Anion with 10-MR Windows and 12-MR Channels - - C. W. Duan, L. X. Hu, J. L. Ma, J. Mater. Chem. A 2018, 6, 6309u20136318  Ionic liquids as an efficient medium for the mechanochemical synthesis of u03b1-AlH3 nano-composites - The cluster is sometimes accompanied by less relevant references and clusters of references. Frequently co-occuring papers include - - Duan CW, Cao YZ, Hu LX, Fu D, Ma JL (2019)  Synergistic effect of TiF3 on the dehydriding property of a-AlH3 nano-composite . - - K. Wang, J. Pang, L. Li, S. Zhou, Y. Li, T. Zhang, Front. Chem. Sci. Eng. 2018, 12, 376u2013382.  Synthesis of hydrophobic carbon nanotubes reduced graphene oxide composite films by flash light irradiation - - K. Wu, K. Du, G. Hu, J. Mater. Chem. A 2018, 6, 1057u20131066  Red-blood-cell-like (NH4) [Fe2(OH)(PO4)2]u00b72H2O particles: Fabrication and application in high-performance LiFePO4 cathode materials - - Yin K, Chu DK, Dong XR, Wang C, Duan JA, He J (2017)  Femtosecond laser induced robust periodic nanoripples structured mesh for highly efficient oil-water separation . Nanoscale 9:14229u201314235. - - Davila-Manzanilla SG, Figueroa-de-Paz Y, Mejia C, Ruiz-Azuara L (2017)  Synergistic effects between a copper-based metal Casiopeu00edna III-Ia and cisplatin . Eur J Med Chem 129:266u2013274 - The vast majority of email identities for corresponding authors were formed by taking an underscore-separated name and appending **666** or 66 . I am advised that these are auspicious numbers with positive associations. So one possibility is that the authors all decided independently to generate email accounts with this format. 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 A subset of these mass-produced papers are further adorned with a small repertoire of **software** references, adding an additional layer of surreal irrelevance.  The early development of postoperative exercise function is inseparable from the adequate postoperative analgesia, especially the analgesic efect of exercise pain [2, 3]. - [2]. H. Li, G. Gao, R. Chen, X. Ge, S. Guo, L.Y. Hao, Int. J. Softw. Eng. Knowl. 29, 93u2013113 (2019) ** The Influence Ranking for Testers in Bug Tracking Systems **  In addition, efective postoperative analgesia can alleviate the stress response, stabilize the patientu2019s internal environment, reduce the patientu2019s anxiety, and improve the short-term quality of life of patients [5]. - [5]. S. Guo, R. Chen, H. Li, T. Zhang, Y. Liu, Int. J. Softw. Eng. Knowl. 29, 139u2013175 (2019) ** Identify Severity Bug Report with Distribution Imbalance by CR-SMOTE and ELM ** ,