title: Cellular uptake of transportan 10 and its analogs in live cells: Selectivity and structure-activity relationship studies.
abstract: Transportan 10 (TP10) is an amphipathic cell-penetrating peptide with high translocation ability. In order to obtain more details of structure-activity relationship of TP10, we evaluated the effects of structure and charge on its translocation ability. Our results demonstrated that disrupting the helical structure or Arg substitution could remarkably decrease the cellular uptake of TP10. However, increasing the number of positive charge was an effective strategy to enhance translocation ability of TP10. Furthermore, the molecular dynamics simulation supported the results derived from experiments, suggesting that higher membrane disturbance leads to higher cellular uptake of peptides. In addition, our study also demonstrated TP10 and its analogs preferentially entered cancer cells rather than normal cells. The uptake selectivity toward cancer cells makes TP10 and its analogs as potent CPPs for drug delivery.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Song
authors.forename: Ming
authors.initials: M
authors.lastname: Kai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jindao
authors.initials: J
authors.lastname: Zhang
authors.forename: Liwei
authors.initials: L
authors.lastname: Liu
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic; D002942:Circular Dichroism; D019004:Galanin / Q000378:metabolism* / Q000633:toxicity; D006367:HeLa Cells; D006461:Hemolysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D051379:Mice; D056004:Molecular Dynamics Simulation; D041681:NIH 3T3 Cells; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism* / Q000633:toxicity; D021241:Spectrometry, Mass, Electrospray Ionization; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000378:metabolism* / Q000633:toxicity
chemical_list: D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D011993:Recombinant Fusion Proteins; D014862:Wasp Venoms; C110068:transportan; D019004:Galanin; D007770:L-Lactate Dehydrogenase