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CPP 2 Cargo or mRNA CAP Antisense AUG TAC AAAAA Decoy + Protein CPP -S-S- 4 Cargo Protein FIGURE 16.1 Schematic illustration of different CPP–cargo conjugates and their intracellular targets. Cargoes reported and reviewed in this chapter are ssDNA, dsDNA, ssPNA, ssPS, dsPS, plasmid. A model of transportan structure (From Lindberg, M. et al., Biochemistry, 40, 3141, 2001. With permission.) is shown as an example of CPP. 1 = denotes the process of internalization of conjugates, 2 = antisense effect of cargo, 3 = antigene effect of cargo, 4 = competitive binding of the ds decoy oligomer to the DNA-binding proteins (transcription factors, etc.), 5 = transfection with plasmid or phage. 1 Nucleus C ytoplasm DNA or or CPP 3 Antigene Decoy Protein expression Plasmid 5 λ Transfection CPP Plasmid or CPP Plasma membrane λ phage Cell-Penetrating Peptides as Vectors for Delivery of Nucleic Acids 359
360 Cell-Penetrating Peptides: Processes and Applications REFERENCES 1. Delihas, N., Rokita, S.E., and Zheng, P., Natural antisense RNA/target RNA interactions: possible models for antisense oligonucleotide drug design, Nat. Biotechnol., 15, 751, 1997. 2. Morishita, R. et al., A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo, Proc. Natl. Acad. Sci. U.S.A., 92, 5855, 1995. 3. Feeley, B.T. et al., Nuclear factor-kappaB transcription factor decoy treatment inhibits graft coronary artery disease after cardiac transplantation in rodents, Transplantation, 70, 1560, 2000. 4. Ishibashi, H. et al., Sp1 decoy transfected to carcinoma cells suppresses the expression of vascular endothelial growth factor, transforming growth factor beta1, and tissue factor and also cell growth and invasion activities, Cancer Res., 60, 6531, 2000. 5. Kawamura, I. et al., Intravenous injection of oligodeoxynucleotides to the NF-kappaB binding site inhibits hepatic metastasis of M5076 reticulosarcoma in mice, Gene Ther., 8, 905, 2001. 6. Tomita, N. et al., Inhibition of TNF-alpha, induced cytokine and adhesion molecule. Expression in glomerular cells in vitro and in vivo by transcription factor decoy for NFkappaB, Exp. Nephrol., 9, 181, 2001. 7. Park, Y.G. et al., Reduction in cyclin D1/Cdk4/retinoblastoma protein signaling by CRE-decoy oligonucleotide, Biochem. Biophys. Res. Commun., 281, 1213, 2001. 8. Deshpande, D. et al., Enhanced cellular uptake of oligonucleotides by EGF receptormediated endocytosis in A549 cells, Pharm. Res., 13, 57, 1996. 9. Nakai, D. et al., Cellular uptake mechanism for oligonucleotides: involvement of endocytosis in the uptake of phosphodiester oligonucleotides by a human colorectal adenocarcinoma cell line, HCT-15, J. Pharmacol. Exp. Ther., 278, 1362, 1996. 10. Bennet, R.M. et al., The production and characterization of murine monoclonal antibodies to a DNA receptor on human leukocytes, J. Immunol., 140, 2937, 1988. 11. Hefeneider, S.H. et al., Identification of a cell-surface DNA receptor and its association with systemic lupus erythematosus, J. Invest. Dermatol., 94, 79S, 1990. 12. Francolini, M. et al., Evidence for nuclear internalization of exogenous DNA into mammalian sperm cells, Mol. Reprod. Dev., 34, 133, 1993. 13. Zamecnik, P. et al., Electron micrographic studies of transport of oligodeoxynucleotides across eukaryotic cell membranes, Proc. Natl. Acad. Sci. U.S.A., 91, 3156, 1994. 14. Goodarzi, G., Watabe, M., and Watabe, K., Binding of oligonucleotides to cell membranes at acidic pH, Biochem. Biophys. Res. Commun., 181, 1343, 1991. 15. Akhtar, S. et al., The influence of polarized epithelial (Caco-2) cell differentiation on the cellular binding of phosphodiester and phosphorothioate oligonucleotides, Antisense Nucleic Acid Drug Dev., 6, 197, 1996. 16. Yakubov, L.A. et al., Mechanism of oligonucleotide uptake by cells: involvement of specific receptors? Proc. Natl. Acad. Sci. U.S.A., 86, 6454, 1989. 17. Wu-Pong, S., Weiss, T.L., and Hunt, C.A., Antisense c-myc oligonucleotide cellular uptake and activity, Antisense Res. Dev., 4, 155, 1994. 18. Wu-Pong, S., Weiss, T.L., and Hunt, C.A., Antisense c-myc oligodeoxyribonucleotide cellular uptake, Pharm. Res., 9, 1010, 1992. 19. Nestle, F.O. et al., Cationic lipid is not required for uptake and selective inhibitory activity of ICAM-1 phosphorothioate antisense oligonucleotides in keratinocytes, J. Invest. Dermatol., 103, 569, 1994.
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CELL- PENETRATING PEPTIDES Processe
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Pharmacology and Toxicology: Basic
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Library of Congress Cataloging-in-P
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to the handbook are prominent resea
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REFERENCES 1. Green, M. and Loewens
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Contributors Mats Andersson Microbi
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Erin T. Pelkey Department of Chemis
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Contents Section I Classes of Cell-
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Chapter 16 Cell-Penetrating Peptide
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The Tat-Derived Cell-Penetrating Pe
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24 Cell-Penetrating Peptides: Proce
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3 Transportans Margus Pooga, Mattia
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Transportans 55 Indeed, galparan is
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Transportans 57 especially the endo
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Transportans 59 In the penetration
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Transportans 61 A 21-mer antisense
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Transportans 63 Commonly, the prote
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Transportans 65 antibiotin antibodi
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Transportans 67 For cross-linking o
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Transportans 69 and still retain ef
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Model Amphipathic Peptides 73 its D
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Model Amphipathic Peptides 75 pmol/
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TABLE 4.1 Internalization of Peptid
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TABLE 4.2 Internalization of Peptid
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Model Amphipathic Peptides 81 relat
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Model Amphipathic Peptides 87 A cat
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Model Amphipathic Peptides 89 At th
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Model Amphipathic Peptides 91 16. H
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Signal Sequence-Based Cell-Penetrat
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116 Cell-Penetrating Peptides: Proc
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Interactions of Cell-Penetrating Pe
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Structure Prediction of CPPs and It
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FIGURE 9.7 (Color Figure 9.7 follow
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FIGURE 9.8 The center of the figure
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Biophysical Studies of Cell-Penetra
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Toxicity and Side Effects of Cell-P
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Kinetics of Uptake of Cell-Penetrat
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Page 350 and 351: Cell-Penetrating Peptide Conjugatio
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Page 422 and 423: Index 401 structure prediction, 187
Page 424 and 425: Index 403 pRB proteins, Tat-E1A bin
Page 426 and 427: Index 405 lipid perturbation (secon
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