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Página principal > Artículos > Artículos publicados > Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides |
Fecha: | 2018 |
Resumen: | 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. |
Ayudas: | Ministerio de Ciencia e Innovación BIO2016-76063-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/PROD0005 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/FI_B100063 Instituto de Salud Carlos III PI15/00272 Instituto de Salud Carlos III PIE15/00028 Instituto de Salud Carlos III PIE15/00378 |
Nota: | Altres ajuts: we are indebted to CIBER de Bioingeniería, Biomateriales y Nanomedicina (project NANOPROTHER) for funding AV. Also, to Marató de TV3 foundation (TV32013-3930). Marató TV3 (2013-2030) granted to RM, for funding research on targeted, protein-based drug delivery. MTPF received a fellowship from Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil (2015/20193-3).NS by a predoctoral fellowship from the Government of Navarra and UU received a Sara Borrell postdoctoral fellowship from ISCIII. AV received an Icrea Academia Award. |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió acceptada per publicar |
Materia: | Protein materials ; Protein engineering ; Self-assembling ; CXCR4 ; Tumor-homing peptides |
Publicado en: | Nanomedicine, Vol. 14, issue 6 (August 2018) , p. 1777-1786, ISSN 1549-9642 |
Postprint 27 p, 438.8 KB |