scholarly journals Overlapping Properties of the Short Membrane-Active Peptide BP100 With (i) Polycationic TAT and (ii) α-helical Magainin Family Peptides

2021 ◽  
Vol 11 ◽  
Author(s):  
Christian Mink ◽  
Erik Strandberg ◽  
Parvesh Wadhwani ◽  
Manuel N. Melo ◽  
Johannes Reichert ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Mechanism Of Action ◽  
Helical Structure ◽  
Lipid Vesicles ◽  
Cell Penetrating Peptides ◽  
Cell Uptake ◽  
Active Peptide ◽  
Hiv Tat ◽  
Cell Penetrating ◽  
Α Helix

BP100 is a short, designer-made membrane-active peptide with multiple functionalities: antimicrobial, cell-penetrating, and fusogenic. Consisting of five lysines and 6 hydrophobic residues, BP100 was shown to bind to lipid bilayers as an amphipathic α-helix, but its mechanism of action remains unclear. With these features, BP100 embodies the characteristics of two distinctly different classes of membrane-active peptides, which have been studied in detail and where the mechanism of action is better understood. On the one hand, its amphiphilic helical structure is similar to the pore forming magainin family of antimicrobial peptides, though BP100 is much too short to span the membrane. On the other hand, its length and high charge density are reminiscent of the HIV-TAT family of cell penetrating peptides, for which inverted micelles have been postulated as translocation intermediates, amongst other mechanisms. Assays were performed to test the antimicrobial and hemolytic activity, the induced leakage and fusion of lipid vesicles, and cell uptake. From these results the functional profiles of BP100, HIV-TAT, and the magainin-like peptides magainin 2, PGLa, MSI-103, and MAP were determined and compared. It is observed that the activity of BP100 resembles most closely the much longer amphipathic α-helical magainin-like peptides, with high antimicrobial activity along with considerable fusogenic and hemolytic effects. In contrast, HIV-TAT shows almost no antimicrobial, fusogenic, or hemolytic effects. We conclude that the amphipathic helix of BP100 has a similar membrane-based activity as magainin-like peptides and may have a similar mechanism of action.

scholarly journals Shape Effects of Nanoparticles Conjugated with Cell-Penetrating Peptides (HIV Tat PTD) on CHO Cell Uptake

2008 ◽  
Vol 19 (9) ◽  
pp. 1880-1887 ◽  
Author(s):  
Ke Zhang ◽  
Huafeng Fang ◽  
Zhiyun Chen ◽  
John-Stephen A. Taylor ◽  
Karen L. Wooley
Keyword(s):  
Cell Penetrating Peptides ◽  
Cell Uptake ◽  
Cho Cell ◽  
Hiv Tat ◽  
Cell Penetrating ◽  
Shape Effects

Arf6-mediated macropinocytosis enhanced suicide gene therapy of C16TAB-condensed Tat/pDNA nanoparticles in ovarian cancer

Nanoscale ◽  
2021 ◽  
Author(s):  
Zhe Sun ◽  
Jinhai Huang ◽  
Linjia Su ◽  
Jing Li ◽  
Fangzheng Qi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Therapy ◽  
Cancer Treatment ◽  
Plasmid Dna ◽  
Suicide Gene ◽  
Cell Penetrating Peptides ◽  
Therapeutic Gene ◽  
Hiv Tat ◽  
Efficient Delivery ◽  
Cell Penetrating

Using cell-penetrating peptides (CPPs), typically HIV-Tat, to deliver the therapeutic gene for cancer treatment has being hampered by low efficient delivery and complicated uptake route of plasmid DNA (pDNA). On...

scholarly journals Bactericidal and membrane disruption activities of the eosinophil cationic protein are largely retained in an N-terminal fragment

2009 ◽  
Vol 421 (3) ◽  
pp. 425-434 ◽  
Author(s):  
Marc Torrent ◽  
Beatriz G. de la Torre ◽  
Victòria M. Nogués ◽  
David Andreu ◽  
Ester Boix
Keyword(s):  
Lipid Bilayers ◽  
Cell Damage ◽  
Eosinophil Cationic Protein ◽  
Lipid Vesicles ◽  
Antimicrobial Activities ◽  
Membrane Disruption ◽  
Structural Determinants ◽  
Cationic Protein ◽  
Native Proteins ◽  
Α Helix

ECP (eosinophil cationic protein) is an eosinophil secretion protein with antipathogen activities involved in the host immune defence system. The bactericidal capacity of ECP relies on its action on both the plasma membrane and the bacterial wall. In a search for the structural determinants of ECP antimicrobial activity, we have identified an N-terminal domain (residues 1–45) that retains most of ECP's membrane-destabilizing and antimicrobial activities. Two sections of this domain, ECP-(1–19) and ECP-(24–45), have also been evaluated. All three peptides bind and partially insert into lipid bilayers, inducing aggregation of lipid vesicles and leakage of their aqueous content. In such an environment, the peptides undergo conformational change, significantly increasing their α-helix content. The bactericidal activity of the three peptides against Escherichia coli and Staphylococcus aureus has been assessed at both the cytoplasmic membrane and the bacterial envelope levels. ECP-(1–45) and ECP-(24–45) partially retain the native proteins ability to bind LPS (lipopolysaccharides), and electron microscopy reveals cell damage by both peptides. Interestingly, in the E. coli cells agglutination activity of ECP is only retained by the longest segment ECP-(1–45). Comparative results suggest a task distribution, whereby residues 1–19 would contribute to membrane association and destabilization, while the 24–45 region would be essential for bactericidal action. Results also indicate that ECP cytotoxicity is not uniquely dependant on its membrane disruption capacity, and that specific interactions at the bacteria wall are also involved.

scholarly journals Transcriptional Profiling Reveals Ribosome Biogenesis, Microtubule Dynamics and Expression of Specific lncRNAs to be Part of a Common Response to Cell-Penetrating Peptides

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1567
Author(s):  
Tomas Venit ◽  
Moataz Dowaidar ◽  
Maxime Gestin ◽  
Syed Raza Mahmood ◽  
Ülo Langel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Bilayers ◽  
Hela Cells ◽  
Ribosome Biogenesis ◽  
Time Course ◽  
Transcriptional Profiling ◽  
Cell Penetrating Peptides ◽  
Microtubule Dynamics ◽  
Cell Penetrating ◽  
Common Response

Cell-penetrating peptides (CPPs) are short peptides that are able to efficiently penetrate cellular lipid bilayers. Although CPPs have been used as carriers in conjugation with certain cargos to target specific genes and pathways, how rationally designed CPPs per se affect global gene expression has not been investigated. Therefore, following time course treatments with 4 CPPs-penetratin, PepFect14, mtCPP1 and TP10, HeLa cells were transcriptionally profiled by RNA sequencing. Results from these analyses showed a time-dependent response to different CPPs, with specific sets of genes related to ribosome biogenesis, microtubule dynamics and long-noncoding RNAs being differentially expressed compared to untreated controls. By using an image-based high content phenotypic profiling platform we confirmed that differential gene expression in CPP-treated HeLa cells strongly correlates with changes in cellular phenotypes such as increased nucleolar size and dispersed microtubules, compatible with altered ribosome biogenesis and cell growth. Altogether these results suggest that cells respond to different cell penetrating peptides by alteration of specific sets of genes, which are possibly part of the common response to such stimulus.

Applications of cell-penetrating peptides in regulation of gene expression

2007 ◽  
Vol 35 (4) ◽  
pp. 770-774 ◽  
Author(s):  
P. Järver ◽  
K. Langel ◽  
S. El-Andaloussi ◽  
Ü. Langel
Keyword(s):  
Gene Expression ◽  
Lipid Bilayers ◽  
Regulation Of Gene Expression ◽  
Cell Penetrating Peptides ◽  
Remarkable Feature ◽  
Cell Penetrating ◽  
Plasmid Delivery ◽  
Interfering Rna

CPPs (cell-penetrating peptides) can be defined as short peptides that are able to efficiently penetrate cellular lipid bilayers. Because of this remarkable feature, they are excellent candidates regarding alterations in gene expression. CPPs have been utilized in in vivo and in vitro experiments as delivery vectors for different bioactive cargoes. This review focuses on the experiments performed in recent years where CPPs have been used as vectors for multiple effectors of gene expression such as oligonucleotides for antisense, siRNA (small interfering RNA) and decoy dsDNA (double-stranded DNA) applications, and as transfection agents for plasmid delivery.

scholarly journals Nucleic acid delivery by cell penetrating peptides derived from dengue virus capsid protein: design and mechanism of action

FEBS Journal ◽  
2013 ◽  
Vol 281 (1) ◽  
pp. 191-215 ◽  
Author(s):  
João M. Freire ◽  
Ana Salomé Veiga ◽  
Inês Rego de Figueiredo ◽  
Beatriz G. de la Torre ◽  
Nuno C. Santos ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Dengue Virus ◽  
Capsid Protein ◽  
Protein Design ◽  
Mechanism Of Action ◽  
Cell Penetrating Peptides ◽  
Nucleic Acid Delivery ◽  
Virus Capsid ◽  
Cell Penetrating ◽  
Virus Capsid Protein

scholarly journals Ionpair-π interactions favor cell penetration of arginine/tryptophan-rich cell-penetrating peptides

2019 ◽  
Author(s):  
Astrid Walrant ◽  
Antonio Bauzá ◽  
Claudia Girardet ◽  
Isabel D. Alves ◽  
Sophie Lecomte ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Density Functional ◽  
Molecular Mechanisms ◽  
Cell Penetrating Peptides ◽  
Membrane Phospholipids ◽  
Active Peptides ◽  
Π Interactions ◽  
Cell Penetrating ◽  
Membrane Active Peptides

AbstractCell-penetrating peptides (CPPs) internalization can occur both by endocytosis and direct translocation through the cell membrane. These different entry routes suggest that molecular partners at the plasma membrane, phospholipids or glycosaminoglycans (GAGs), bind CPPs with different affinity or selectivity. The analysis of sequence-dependent interactions of CPPs with lipids and GAGs should lead to a better understanding of the molecular mechanisms underlying their internalization. CPPs are short sequences generally containing a high number of basic arginines and lysines and sometimes aromatic residues, in particular tryptophans. Tryptophans are crucial residues in membrane-active peptides, because they are important for membrane interaction. Membrane-active peptides often present facial amphiphilicity, which also promote the interaction with lipid bilayers. To study the role of Trp and facial amphiphilicity in cell interaction and penetration of CPPs, a nonapeptide series containing only Arg, Trp or D-Trp residues at different positions was designed. Our quantitative study indicates that to maintain/increase the uptake efficiency, Arg can be advantageously replaced by Trp in the nonapeptides. The presence of Trp in oligoarginines increases the uptake in cells expressing GAGs at their surface, when it only compensates for the loss of Arg and maintains similar peptide uptake in GAG-deficient cells. In addition, we show that facial amphiphilicity is not required for efficient uptake of these nonapeptides. Thermodynamic analyses point towards a key role of Trp that highly contributes to the binding enthalpy of complexes formation. Density functional theory (DFT) analysis highlights that salt bridge-π interactions play a crucial role for the GAG-dependent entry mechanisms.

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