Analysis of in vitro toxicity of five cell-penetrating peptides by metabolic profiling

Kilk, Kalle; Mahlapuu, Riina; Soomets, Ursel; Langel, Ülo

doi:10.1016/j.tox.2009.09.016

Cited by 82 publications

(57 citation statements)

References 36 publications

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“…If so, those CPPs may affect mitochondria function. In agreement with this idea, a recent metabolomic analysis comparing the toxic potential of four CPPs (transportan, penetratin, HIV Tat derived peptide, and nona-arginine) showed the toxicity of transportan (36), suggesting the potential CAP activity of transportan. The toxicity was estimated by the effect on cellular redox potential and energy depletion, both related to mitochondria function.…”

Section: Discussionmentioning

confidence: 57%

Cell Penetrating Peptides and Cationic Antibacterial Peptides

Plaza

Morales‐Nava

Diener

et al. 2014

Journal of Biological Chemistry

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Background: Iztli peptides (IP) are a new class of antibacterial peptides that could be internalized by receptor-mediated endocytosis in yeast. Results: IP-1 penetrates cells independently of endocytosis and makes pores in membranes with large electric potential. Conclusion: Antibacterial peptides like IP-1 make pores or penetrate membranes depending on the membrane potential. Significance: Antibacterial peptides with penetrating activity are robust to control bacterial infections.

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Section: Discussionmentioning

confidence: 57%

Cell Penetrating Peptides and Cationic Antibacterial Peptides

Plaza

Morales‐Nava

Diener

et al. 2014

Journal of Biological Chemistry

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“…Another drawback of CPPs such as the TAT peptide is that they affect target cells, e.g., by influencing the metabolic profile (Kilk et al 2009) or by modulating gene expression (Moschos et al 2007). The application of specific domains of bacterial protein toxins as cellular delivery vehicles is well established and led to the development of so-called immunotoxins for cancer therapy (Pastan et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Internalization of biotinylated compounds into cancer cells is promoted by a molecular Trojan horse based upon core streptavidin and clostridial C2 toxin

Fahrer

Funk

Lillich

et al. 2010

Naunyn-Schmied Arch Pharmacol

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The C2 toxin produced by Clostridium botulinum is a binary AB-type exotoxin composed of the enzyme subunit C2I and the binding/translocation moiety C2II. After proteolytic activation, C2IIa mediates the subsequent internalization of C2I into the cytosol of mammalian target cells. The N-terminal domain of C2I (C2IN) is necessary for C2IIa-dependent uptake, but lacks the enzyme domain that is responsible for cytotoxicity. In the present study, we generated a delivery system building on C2IN and a truncated core streptavidin (Stv13) with enhanced solubility for the C2IIa-dependent internalization of biotinylated cargo molecules into mammalian cells. C2IN-Stv13 fusion protein expressed in Escherichia coli was obtained in high yields and purity. The affinity-purified protein formed tetramers and a defined higher order species in solution as shown by gel filtration and retained its biotin-binding properties, however with an obvious reduction in affinity. Uptake of C2IN-Stv13 into the cytosol of HeLa and other cancer cell lines was observed by immunoblot analysis, which was corroborated by confocal microscopy. In addition, the fusion protein was not cytotoxic and did not inhibit cell proliferation as determined by MTS assay. Finally, we demonstrated the C2IN-Stv13/C2IIa-mediated uptake of biocytin-Alexa 488 as cargo into HeLa cells, underscoring the functionality of the generated transport system.

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“…The lower number of positively charged residues of V comparing with Tat might be responsible for its lower cytotoxicity (Chung et al, 2007). The higher alteration of cytosolic metabolome in CHO cells by Tat resulting in the higher cytotoxicity comparing with other CPPs such as penetratin and nona-arginine (R 9 ) has also been reported (Kilk et al, 2009). In comparing with single peptides, almost all mixtures showed lower cytotoxicity than GFP or Tat but not V in both cells.…”

Section: Discussionmentioning

confidence: 91%

“…Several studies demonstrated successful oral peptide drugs delivery by Tat, such as an increase in intestinal absorption of insulin by coupling with Tat via SMCC linkage or co-administered with oligoarginine (Liang & Yang, 2005;Kamei et al, 2008). However, the cytotoxic effects of this peptide including neurotoxicity if it could reach the neuron in comparing with other CPPs have been reported (Strijbos et al, 1995;Kilk et al, 2009).…”

Section: Original Articlementioning

confidence: 99%