Abstract
Cell penetrating peptides (CPPs) have been proven to be an effective vector to deliver a variety of membrane-impermeable macromolecules, such as DNAs, siRNAs, and proteins. Conventional single-chain CPPs typically suffer from severe protease degradation and fast clearance rate for in vivo therapeutic delivery application. In this chapter, we show that supramolecular assembly of de novo designed cationic multidomain peptides (MDPs) leads to nanostructured filaments with increased proteolytic stability and potent membrane activity necessary for improved transfection efficiency.
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References
Frankel AD, Pabo CO (1988) Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55:1189–1193
Green M, Ishino M, Loewenstein PM (1989) Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression. Cell 58:215–223
Vives E, Brodin P, Lebleu B (1997) A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J Biol Chem 272:16010–16017
Jiang T, Olson ES, Nguyen QT, Roy M, Jennings PA, Tsien RY (2004) Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc Natl Acad Sci U S A 101:17867–17872
Fosgerau K, Hoffmann T (2015) Peptide therapeutics: current status and future directions. Drug Discov Today 20:122–128
Dong H, Paramonov SE, Aulisa L, Bakota EL, Hartgerink JD (2007) Self-assembly of multidomain peptides: balancing molecular frustration controls conformation and nanostructure. J Am Chem Soc 129:12468–12472
Som A, Tezgel AO, Gabriel GJ, Tew GN (2011) Self-activation in de novo designed mimics of cell-penetrating peptides. Angew Chem Int Ed 50:6147–6150
Som A, Reuter A, Tew GN (2012) Protein transduction domain mimics: the role of aromatic functionality. Angew Chem Int Ed 51:980–983
Lu H, Wang J, Bai Y, Lang JW, Liu S, Lin Y, Cheng J (2011) Ionic polypeptides with unusual helical stability. Nat Commun 2:206
Yin L, Song Z, Kim KH, Zheng N, Tang H, Lu H, Gabrielson N, Cheng J (2013) Reconfiguring the architectures of cationic helical polypeptides to control non-viral gene delivery. Biomaterials 34:2340–2349
Xu D, Jiang L, Singh A, Dustin D, Yang M, Liu L, Lund R, Sellati TJ, Dong H (2015) Designed supramolecular filamentous peptides: balance of nanostructure, cytotoxicity and antimicrobial activity. Chem Commun 51:1289–1292
Xu D, Dustin D, Jiang L, Samways DSK, Dong H (2015) Designed filamentous cell penetrating peptides: probing supramolecular structure-dependent membrane activity and transfection efficiency. Chem Commun 51:11757–11760
Yang M, Xu D, Jiang L, Zhang L, Dustin D, Lund R, Liu L, Dong H (2014) Filamentous supramolecular peptide-drug conjugates as highly efficient drug delivery vehicles. Chem Commun 50:4827–4830
Bukhari M, Deng H, Jones N, Towne Z, Woodworth CD, Samways DSK (2015) Selective permeabilization of cervical cancer cells to an ionic DNA-binding cytotoxin by activation of P2Y receptors. FEBS Lett 589:1498–1504
Zheng N, Yin L, Song Z, Ma L, Tang H, Gabrielson NP, Lu H, Cheng J (2014) Maximizing gene delivery efficiencies of cationic helical polypeptides via balanced membrane penetration and cellular targeting. Biomaterials 35:1302–1314
Manthorpe M, Cornefert-Jensen F, Hartikka J, Felgner J, Rundell A, Margalith M, Dwarki V (1993) Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum Gene Ther 4:419–431
Acknowledgments
Clarkson University is acknowledged for the support of this work. We thank the Clarkson-Trudeau Partnership for providing seed fund to support this project. This study was supported by the National Science Foundation (DMR 1654426).
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Xu, D., DeRidder, L., Elmore, B., Dong, H. (2018). Self-assembly of Filamentous Cell Penetrating Peptides for Gene Delivery. In: Nilsson, B., Doran, T. (eds) Peptide Self-Assembly. Methods in Molecular Biology, vol 1777. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7811-3_17
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DOI: https://doi.org/10.1007/978-1-4939-7811-3_17
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