title: Cellular translocation of a γ-AApeptide mimetic of Tat peptide.
abstract: Cell-penetrating peptides including the trans-activating transcriptional activator (Tat) from HIV-1 have been used as carriers for intracellular delivery of a myriad of cargoes including drugs, molecular probes, DNAs and nanoparticles. Utilizing fluorescence flow cytometry and confocal fluorescence microscopy, we demonstrate that a γ-AApeptide mimetic of Tat (48-57) can cross the cell membranes and enter the cytoplasm and nucleus of cells, with efficiency comparable to or better than that of Tat peptide (48-57). Deletion of the four side chains of the γ-AApeptide attenuates translocation capability. We also establish that the γ-AApeptide is even less toxic than the Tat peptide against mammalian cells. In addition to their low toxicity, γ-AApeptides are resistant to protease degradation, which may prove to be advantageous over α-peptides for further development of molecular transporters for intracellular delivery.
authors.affiliation: Department of Chemistry, University of South Florida, Tampa, Florida 33620, United States.
authors.forename: Youhong
authors.initials: Y
authors.lastname: Niu
authors.forename: Ge
authors.initials: G
authors.lastname: Bai
authors.forename: Haifan
authors.initials: H
authors.lastname: Wu
authors.forename: Rongsheng E
authors.initials: RE
authors.lastname: Wang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Qiao
authors.forename: Shruti
authors.initials: S
authors.lastname: Padhee
authors.forename: Robert
authors.initials: R
authors.lastname: Buzzeo
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Cao
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
mesh_terms: D002460:Cell Line; D057846:Cell-Penetrating Peptides; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D021381:Protein Transport; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D010446:Peptide Fragments; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus; C520542:tat peptide (48-57), Human immunodeficiency virus 1