Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes
Cell-penetrating peptides (CPPs) have emerged as versatile tools to increase the intracellular accumulation of different kinds of cargoes. For an efficient cellular uptake and drug delivery, their organization into a distinct and stable secondary structure at the outer surface of the plasma membrane...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/12/2075 |
| _version_ | 1797501491944095744 |
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| author | Tamara Lützenburg Nele Burdina Matthias S. Scholz Ines Neundorf |
| author_facet | Tamara Lützenburg Nele Burdina Matthias S. Scholz Ines Neundorf |
| author_sort | Tamara Lützenburg |
| collection | DOAJ |
| description | Cell-penetrating peptides (CPPs) have emerged as versatile tools to increase the intracellular accumulation of different kinds of cargoes. For an efficient cellular uptake and drug delivery, their organization into a distinct and stable secondary structure at the outer surface of the plasma membrane is a hallmark and supports optimal lipid–peptide interactions. Incorporation of hydrophobic moieties, such as carboranes (CBs), has the potential to increase the lipophilicity of peptides, and thus, to facilitate the formation of secondary structures. Herein, we present synthesis and biophysical as well as biological characterization of carborane-CPP conjugates having incorporated one or more CB clusters. Our results highlight the possibility to modulate the secondary structure of CPPs by the addition of CB’s leading to constructs with altered membrane activity and promising use in terms of nucleic acid delivery. |
| first_indexed | 2024-03-10T03:19:11Z |
| format | Article |
| id | doaj.art-22c21d5d9add4cb5b50292ab969d07c0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:19:11Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-22c21d5d9add4cb5b50292ab969d07c02023-11-23T10:05:34ZengMDPI AGPharmaceutics1999-49232021-12-011312207510.3390/pharmaceutics13122075Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with CarboranesTamara Lützenburg0Nele Burdina1Matthias S. Scholz2Ines Neundorf3Institute for Biochemistry, Department of Chemistry, University of Cologne, Zülpicher Str. 47a, 50674 Cologne, GermanyInstitute for Biochemistry, Department of Chemistry, University of Cologne, Zülpicher Str. 47a, 50674 Cologne, GermanyPharmaceutical Chemistry I & II, Pharmaceutical Institute, Faculty of Mathematics and Natural Sciences, University of Bonn, An der Immenburg 4, 53121 Bonn, GermanyInstitute for Biochemistry, Department of Chemistry, University of Cologne, Zülpicher Str. 47a, 50674 Cologne, GermanyCell-penetrating peptides (CPPs) have emerged as versatile tools to increase the intracellular accumulation of different kinds of cargoes. For an efficient cellular uptake and drug delivery, their organization into a distinct and stable secondary structure at the outer surface of the plasma membrane is a hallmark and supports optimal lipid–peptide interactions. Incorporation of hydrophobic moieties, such as carboranes (CBs), has the potential to increase the lipophilicity of peptides, and thus, to facilitate the formation of secondary structures. Herein, we present synthesis and biophysical as well as biological characterization of carborane-CPP conjugates having incorporated one or more CB clusters. Our results highlight the possibility to modulate the secondary structure of CPPs by the addition of CB’s leading to constructs with altered membrane activity and promising use in terms of nucleic acid delivery.https://www.mdpi.com/1999-4923/13/12/2075alpha-helix stabilizationsecondary structurecell-penetrating peptideslipid–peptide interactionpeptide engineering |
| spellingShingle | Tamara Lützenburg Nele Burdina Matthias S. Scholz Ines Neundorf Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes Pharmaceutics alpha-helix stabilization secondary structure cell-penetrating peptides lipid–peptide interaction peptide engineering |
| title | Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes |
| title_full | Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes |
| title_fullStr | Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes |
| title_full_unstemmed | Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes |
| title_short | Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes |
| title_sort | improving membrane activity and cargo delivery efficacy of a cell penetrating peptide by loading with carboranes |
| topic | alpha-helix stabilization secondary structure cell-penetrating peptides lipid–peptide interaction peptide engineering |
| url | https://www.mdpi.com/1999-4923/13/12/2075 |
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