Selective Moonlighting Cell-Penetrating Peptides
Cell penetrating peptides (CPPs) are molecules capable of passing through biological membranes. This capacity has been used to deliver impermeable molecules into cells, such as drugs and DNA probes, among others. However, the internalization of these peptides lacks specificity: CPPs internalize indi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/8/1119 |
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| author | Rafael Morán-Torres David A. Castillo González Maria Luisa Durán-Pastén Beatriz Aguilar-Maldonado Susana Castro-Obregón Gabriel Del Rio |
| author_facet | Rafael Morán-Torres David A. Castillo González Maria Luisa Durán-Pastén Beatriz Aguilar-Maldonado Susana Castro-Obregón Gabriel Del Rio |
| author_sort | Rafael Morán-Torres |
| collection | DOAJ |
| description | Cell penetrating peptides (CPPs) are molecules capable of passing through biological membranes. This capacity has been used to deliver impermeable molecules into cells, such as drugs and DNA probes, among others. However, the internalization of these peptides lacks specificity: CPPs internalize indistinctly on different cell types. Two major approaches have been described to address this problem: (i) targeting, in which a receptor-recognizing sequence is added to a CPP, and (ii) activation, where a non-active form of the CPP is activated once it interacts with cell target components. These strategies result in multifunctional peptides (i.e., penetrate and target recognition) that increase the CPP’s length, the cost of synthesis and the likelihood to be degraded or become antigenic. In this work we describe the use of machine-learning methods to design short selective CPP; the reduction in size is accomplished by embedding two or more activities within a single CPP domain, hence we referred to these as moonlighting CPPs. We provide experimental evidence that these designed moonlighting peptides penetrate selectively in targeted cells and discuss areas of opportunity to improve in the design of these peptides. |
| first_indexed | 2024-03-10T08:28:54Z |
| format | Article |
| id | doaj.art-0413ea7315124937821d2d37de30caf7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T08:28:54Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0413ea7315124937821d2d37de30caf72023-11-22T09:12:44ZengMDPI AGPharmaceutics1999-49232021-07-01138111910.3390/pharmaceutics13081119Selective Moonlighting Cell-Penetrating PeptidesRafael Morán-Torres0David A. Castillo González1Maria Luisa Durán-Pastén2Beatriz Aguilar-Maldonado3Susana Castro-Obregón4Gabriel Del Rio5Department of Biochemistry and Structural Biology, Institute of Cellular Physiology, National Autonomous University of Mexico, UNAM, Mexico City 04510, MexicoDepartment of Biochemistry and Structural Biology, Institute of Cellular Physiology, National Autonomous University of Mexico, UNAM, Mexico City 04510, MexicoLaboratorio Nacional de Canalopatias, National Autonomous University of Mexico, UNAM, Mexico City 04510, MexicoDepartment of Neurodevelopment and Physiology, Institute of Cellular Physiology, National Autonomous University of Mexico, Mexico City 04510, MexicoDepartment of Neurodevelopment and Physiology, Institute of Cellular Physiology, National Autonomous University of Mexico, Mexico City 04510, MexicoDepartment of Biochemistry and Structural Biology, Institute of Cellular Physiology, National Autonomous University of Mexico, UNAM, Mexico City 04510, MexicoCell penetrating peptides (CPPs) are molecules capable of passing through biological membranes. This capacity has been used to deliver impermeable molecules into cells, such as drugs and DNA probes, among others. However, the internalization of these peptides lacks specificity: CPPs internalize indistinctly on different cell types. Two major approaches have been described to address this problem: (i) targeting, in which a receptor-recognizing sequence is added to a CPP, and (ii) activation, where a non-active form of the CPP is activated once it interacts with cell target components. These strategies result in multifunctional peptides (i.e., penetrate and target recognition) that increase the CPP’s length, the cost of synthesis and the likelihood to be degraded or become antigenic. In this work we describe the use of machine-learning methods to design short selective CPP; the reduction in size is accomplished by embedding two or more activities within a single CPP domain, hence we referred to these as moonlighting CPPs. We provide experimental evidence that these designed moonlighting peptides penetrate selectively in targeted cells and discuss areas of opportunity to improve in the design of these peptides.https://www.mdpi.com/1999-4923/13/8/1119cell-penetrating peptidemachine learningmoonlight proteincomputational biologyprotein function predictionmultifunctional protein |
| spellingShingle | Rafael Morán-Torres David A. Castillo González Maria Luisa Durán-Pastén Beatriz Aguilar-Maldonado Susana Castro-Obregón Gabriel Del Rio Selective Moonlighting Cell-Penetrating Peptides Pharmaceutics cell-penetrating peptide machine learning moonlight protein computational biology protein function prediction multifunctional protein |
| title | Selective Moonlighting Cell-Penetrating Peptides |
| title_full | Selective Moonlighting Cell-Penetrating Peptides |
| title_fullStr | Selective Moonlighting Cell-Penetrating Peptides |
| title_full_unstemmed | Selective Moonlighting Cell-Penetrating Peptides |
| title_short | Selective Moonlighting Cell-Penetrating Peptides |
| title_sort | selective moonlighting cell penetrating peptides |
| topic | cell-penetrating peptide machine learning moonlight protein computational biology protein function prediction multifunctional protein |
| url | https://www.mdpi.com/1999-4923/13/8/1119 |
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