@article{a7182be862bd4ea19351c66e3b0d4fad,
title = "Drug conjugation induced modulation of structural and membrane interaction features of cationic cell-permeable peptides",
abstract = "Cell-penetrating peptides might have great potential for enhancing the therapeutic effect of drug molecules against such dangerous pathogens as Mycobacterium tuberculosis (Mtb), which causes a major health problem worldwide. A set of cationic cell-penetration peptides with various hydrophobicity were selected and synthesized as drug carrier of isoniazid (INH), a first-line antibacterial agent against tuberculosis. Molecular interactions between the peptides and their INH-conjugates with cell-membrane-forming lipid layers composed of DPPC and mycolic acid (a characteristic component of Mtb cell wall) were evaluated, using the Langmuir balance technique. Secondary structure of the INH conjugates was analyzed and compared to that of the native peptides by circular dichroism spectroscopic experiments performed in aqueous and membrane mimetic environment. A correlation was found between the conjugation induced conformational and membrane affinity changes of the INH–peptide conjugates. The degree and mode of interaction were also characterized by AFM imaging of penetrated lipid layers. In vitro biological evaluation was performed with Penetratin and Transportan conjugates. Results showed similar internalization rate into EBC-1 human squamous cell carcinoma, but markedly different subcellular localization and activity on intracellular Mtb.",
keywords = "Atomic force microscopy, Cell-penetrating peptides, Circular dichroism spectroscopy, Drug, Langmuir monolayer, Membrane affinity, Mycolic acid, Peptide conjugates",
author = "Edit P{\'a}ri and Kata Horv{\'a}ti and Szilvia B{\H o}sze and Be{\'a}ta Biri-Kov{\'a}cs and B{\'a}lint Szeder and Ferenc Zsila and {\'E}va Kiss",
note = "Funding Information: Funding: This work was financed by the ELTE Institutional Excellence Program (NKFIH-1157-8/2019-DT), which is supported by the Hungarian Ministry of Human Capacities; by the ELTE Thematic Excellence Programme supported by the Hungarian Ministry for Innovation and Technology; and by grants from the European Union and the State of Hungary, co-financed by the European Regional Development Fund (VEKOP-2.3.3-15-2017-00020, VEKOP-2.3.2-16-2017-00014). Project no. 2018-1.2.1-NKP-2018-00005 was implemented with the support provided from the National Research Development and Innovation Fund of Hungary. Funding Information: Acknowledgments: Authors thank L{\'a}szl{\'o} Buday for the confocal microscopy; Gitta Schlosser for the HRMS measurements; Zsuzsa Senoner, S{\'a}ndor D{\'a}vid, Zolt{\'a}n Kis, Bernadett P{\'a}lyi, Judit Henczk{\'o} and N{\'o}ra Magyar for the mycobacterial work and the BSL-3 laboratory guide. K. Horv{\'a}ti was supported by the Premium Postdoctoral Research Program 2019 of the Hungarian Academy of Sciences. E. P{\'a}ri was supported by the {\'U}NKP-19-3 New National Excellence Program of the Ministry for Innovation and Technology. F. Zsila acknowledges the support of the National Competitiveness and Excellence Program (NVKP_16-1-2016-0007) and the BIONANO_GINOP-2.3.2-15-2016-00017b project. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = mar,
day = "22",
doi = "10.3390/ijms21062197",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI",
number = "6",
}
