Title:
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Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides
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Author:
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Teixeira De Pinho Favaro, Marianna; Serna, Naroa; Sanchez Garcia, Laura; Cubarsí Morera, Rafael; Roldan, Monica; Sanchez Chardi, Alejandro; Unzueta, Ugutz; Mangues, Ramón; Ferrer Miralles, Neus; Rodrigues Azzoni, Adriano; Vazquez Gómez, Esther; Villaverde, Antonio
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Other authors:
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Universitat Politècnica de Catalunya. Departament de Matemàtiques |
Abstract:
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Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches. |
Abstract:
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Peer Reviewed |
Subject(s):
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-Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències -Àrees temàtiques de la UPC::Matemàtiques i estadística::Probabilitat -Combinatorial probabilities -Numerical analysis--Simulation methods -Protein materials -Protein engineering -Self-assembling -CXCR4 -Tumor-homing peptides -Anàlisi numèrica -Probabilitats -Classificació AMS::60 Probability theory and stochastic processes::60C05 Combinatorial probability -Classificació AMS::65 Numerical analysis::65C Probabilistic methods, simulation and stochastic differential equations |
Rights:
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Document type:
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Article - Submitted version Article |
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