RESUMO
Cell-penetrating peptides such as antennapedia, TAT, transportan and polyarginine have been extensively employed for in vitro and in vivo delivery of biologically active peptides. However, little is known of the relative efficacy, toxicity and uptake mechanism of individual protein transduction domain-peptide conjugates, factors that will be critical in determining the most effective sequence. In the present study, we show by FACS analysis that unconjugated antennapedia, TAT, transportan and polyarginine demonstrate similar kinetic uptake profiles, being maximal at 1-3 h and independent of cell type (HeLa, A549 and CHO cell lines). A comparison of the magnitude of uptake of cell-penetrating peptide conjugates demonstrated that polyarginine=transportan>antennapedia>TAT. However, examination of cellular toxicity showed that antennapediaAssuntos
Portadores de Fármacos/farmacocinética
, Fragmentos de Peptídeos/farmacocinética
, Sequência de Aminoácidos
, Animais
, Células CHO
, Contagem de Células
, Técnicas de Cultura de Células
, Linhagem Celular Tumoral
, Sobrevivência Celular/efeitos dos fármacos
, Cricetinae
, Portadores de Fármacos/química
, Portadores de Fármacos/toxicidade
, Endocitose/efeitos dos fármacos
, Galanina/química
, Galanina/farmacocinética
, Galanina/toxicidade
, Produtos do Gene tat/química
, Produtos do Gene tat/farmacocinética
, Produtos do Gene tat/toxicidade
, Humanos
, Dados de Sequência Molecular
, Fragmentos de Peptídeos/química
, Fragmentos de Peptídeos/toxicidade
, Peptídeos/química
, Peptídeos/farmacocinética
, Peptídeos/toxicidade
, Proteínas Recombinantes de Fusão/química
, Proteínas Recombinantes de Fusão/farmacocinética
, Proteínas Recombinantes de Fusão/toxicidade
, Venenos de Vespas/química
, Venenos de Vespas/farmacocinética
, Venenos de Vespas/toxicidade
RESUMO
Early studies with protein transduction domains (PTDs), such as those derived from Tat and Drosophila Antennapedia, showed rapid, receptor- and endosomal-independent uptake of conjugated biological tools into all cell types. However, recent mechanistic studies suggest that these observations were artefacts of the positively charged nature of PTDs and that uptake is instead via electrostatic binding to the plasma membrane and subsequent endocytosis. Given these observations, we assess the future utility of PTDs for in vitro and in vivo cellular delivery.