Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation

Åmand, Helene L.; Nordén, Bengt; Fant, Kristina

doi:10.1016/j.bbrc.2012.01.041

Cited by 44 publications

(33 citation statements)

References 32 publications

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“…Penetratin, and HIV-TAT have been successfully used for the formation of non-covalent complexes [11,12,13,14]. Pep, MPG, and CADY peptides were designed by Heitz and Divita for this purpose over a period of about two decades starting with Pep-1[15].…”

Section: Resultsmentioning

confidence: 99%

Relationships between Cargo, Cell Penetrating Peptides and Cell Type for Uptake of Non-Covalent Complexes into Live Cells

et al. 2013

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Modulating signaling pathways for research and therapy requires either suppression or expression of selected genes or internalization of proteins such as enzymes, antibodies, nucleotide binding proteins or substrates including nucleoside phosphates and enzyme inhibitors. Peptides, proteins and nucleotides are transported by fusing or conjugating them to cell penetrating peptides or by formation of non-covalent complexes. The latter is often preferred because of easy handling, uptake efficiency and auto-release of cargo into the live cell. In our studies complexes are formed with labeled or readily detectable cargoes for qualitative and quantitative estimation of their internalization. Properties and behavior of adhesion and suspension vertebrate cells as well as the protozoa Leishmania tarentolae are investigated with respect to proteolytic activity, uptake efficiency, intracellular localization and cytotoxicity. Our results show that peptide stability to membrane-bound, secreted or intracellular proteases varies between different CPPs and that the suitability of individual CPPs for a particular cargo in complex formation by non-covalent interactions requires detailed studies. Cells vary in their sensitivity to increasing concentrations of CPPs. Thus, most cells can be efficiently transduced with peptides, proteins and nucleotides with intracellular concentrations in the low micromole range. For each cargo, cell type and CPP the optimal conditions must be determined separately.

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Section: Resultsmentioning

confidence: 99%

Relationships between Cargo, Cell Penetrating Peptides and Cell Type for Uptake of Non-Covalent Complexes into Live Cells

et al. 2013

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“…Especially, HR9 showed the best transfection efficiency in all cells/organisms we tested so far. We explained that this excellent activity of cellular transport of HR9 may be due to: (1) its specific character of the direct membrane penetration (Dai et al, 2011a;Liu et al, 2011), (2) the addition of polyhistidine in HR9 to protect DNA in the cytoplasm and facilitate DNA endosomal escape (Dai et al, 2011b;Lo and Wang, 2008), and (3) the addition of terminal cysteines in HR9 to polymerize HR9 peptides by disulfide bonds and increase peptide affinity for DNA by the "chelate effect" (Amand et al, 2012).…”

Section: Discussionmentioning

confidence: 96%

Arginine-rich cell-penetrating peptides deliver gene into living human cells

Liu¹,

Lin²,

Chiang³

et al. 2012

Gene

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“…Peptide engineering offers a great opportunity to improve CPP functions, for example, adding C-terminal cysteine to penetratin and its arginine enriched variant markedly enhances peptide affinity to DNA and the stability of the complex, which noticeably improves CPP function as a nucleic acid vector. 12 …”

Section: Introductionmentioning

confidence: 99%

Spontaneous Membrane-Translocating Peptide Adsorption at Silica Surfaces: A Molecular Dynamics Study

et al. 2013

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Spontaneous membrane-translocating peptides (SMTPs) have recently been shown to directly penetrate cell membranes. Adsorption of a SMTP, and some engineered extensions, at model silica surfaces is studied herein using fully atomistic molecular dynamics simulations in order to assess their potential to construct novel drug delivery systems. The simulations are designed to reproduce the electric fields above single, siloxide-rich charged surfaces, and the trajectories indicate that the main driving force for adsorption is electrostatic. An increase in the salt concentration slows down but does not prevent adsorption of the SMTP to the surface; it also does not result in peptide desorption, suggesting additional binding via hydrophobic forces. The results are used to design extensions to the peptide sequence which we find enhance adsorption but do not affect the adsorbed conformation. We also investigate the effect of surface hydroxylation on the peptide adsorption. In all cases, the final adsorbed conformations are with the peptide flattened to the surface with arginine residues, which are key to the peptide’s function, anchoring it to the surface so that they are not exposed to solution. This conformation could impact their role in membrane translocation and thus has important implications for the design of future drug delivery vehicles.

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Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation

Cited by 44 publications

References 32 publications

Relationships between Cargo, Cell Penetrating Peptides and Cell Type for Uptake of Non-Covalent Complexes into Live Cells

Relationships between Cargo, Cell Penetrating Peptides and Cell Type for Uptake of Non-Covalent Complexes into Live Cells

Arginine-rich cell-penetrating peptides deliver gene into living human cells

Spontaneous Membrane-Translocating Peptide Adsorption at Silica Surfaces: A Molecular Dynamics Study

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