Insights on the structural characteristics of Vim-TBS (58-81) peptide for future applications as a cell penetrating peptide

Saini, Avneet; Jaswal, Radhika R.; Negi, Riteshwari; Nandel, Fateh S.

doi:10.5582/bst.2013.v7.5.209

Cited by 5 publications

(4 citation statements)

References 61 publications

(116 reference statements)

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“…Computational techniques are especially powerful for examining the conformation, orientation, and lipid interactions of the peptide in the membrane at atomic level detail. Different studies have shown that the peptides rapidly fold into predominantly helical configuration giving details on the positions of different residues [ 295 , 296 ]. These simulations further tell if the preferred orientation of the peptide is parallel or perpendicular to the membrane normal and if salt bridges are responsible for stabilizing this orientation [ 295 , 297 ].…”

Section: Computer Simulationsmentioning

confidence: 99%

Membrane Active Peptides and Their Biophysical Characterization

2018

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In the last 20 years, an increasing number of studies have been reported on membrane active peptides. These peptides exert their biological activity by interacting with the cell membrane, either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. Membrane active peptides are attractive alternatives to currently used pharmaceuticals and the number of antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery in the drug pipeline is increasing. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). Antimicrobial peptides are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus, and fungi. Cell penetrating peptides are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity. Biophysical techniques shed light on peptide–membrane interactions at higher resolution due to the advances in optics, image processing, and computational resources. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Live imaging techniques allow examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provide clues on the peptide–lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

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Section: Computer Simulationsmentioning

confidence: 99%

Membrane Active Peptides and Their Biophysical Characterization

2018

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“…With the goal to enhance both the transport and internalization of therapeutic agents in hypo-vascularized tumor tissue, in this study we evaluate a variety of poly(lactic-co-glycolic) acid (PLGA) NP formulations for tissue penetration and cellular internalization. The NPs were modified with either a cell penetrating peptide (MPG), a stealth ligand (PEG), a tumor targeting cell penetrating peptide (Vimentin tubulin binding site peptide, VIM) [ 50 , 51 ], or a hybrid modification with both cell penetrating peptides and stealth ligands (MPG/PEG). These ligands were chosen because they have already been individually well characterized to enhance cell internalization, e.g., as we have previously shown for MPG [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced uptake and transport of PLGA-modified nanoparticles in cervical cancer

et al. 2016

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BackgroundUncoordinated cellular proliferation and dysregulated angiogenesis in solid tumors are coupled with inadequate tissue, blood, and lymphatic vascularization. Consequently, tumors are often characterized by hypoxic regions with limited access to vascular-borne substances. In particular, systemically administered nanoparticles (NPs) targeting tumor cells and relying on vascular access to reach tumor tissue can suffer from limited therapeutic efficacy due to inhomogeneous intra-tumor distribution and insufficient cellular internalization of NPs. To circumvent these challenges, NP surfaces can be modified to facilitate tumor interstitial transport and cellular uptake.ResultsWe create poly(lactic-co-glycolic) acid NPs modified with MPG, polyethylene glycol (PEG), MPG/PEG, and Vimentin (VIM), and evaluate their cellular uptake in 2D (monolayer) cell culture of human cervical carcinoma (HeLa). We compare NP performance by evaluating uptake by non-cancerous vaginal (VK2) cells. We further assess NP interstitial transport in hypo-vascularized lesions by evaluating the effect of the various modifications on NP penetration in 3D cell culture of the HeLa cells. Results show that after 24 h incubation with HeLa cells in monolayer, MPG, MPG/PEG, PEG, and VIM NPs were internalized at 66×, 24×, 30×, and 15× that of unmodified NPs, respectively. In contrast, incubation with VK2 cells in monolayer showed that MPG , MPG/PEG , PEG , and VIM NPs internalized at 6.3×, 4.3×, 12.4×, and 3.0× that of unmodified NPs, respectively. Uptake was significantly enhanced in tumorigenic vs. normal cells, with internalization of MPG NPs by HeLa cells being twice that of PEG NPs by VK2 cells. After 24 h incubation in HeLa 3D cell culture, MPG and MPG/PEGNPs were internalized 2× and 3× compared to PEG and VIM NPs, respectively. Whereas MPG NPs were internalized mostly in the cell culture periphery (1.2×, 1.4×, and 2.7× that of PEG, MPG/PEG, and VIM NPs, respectively), PEG NPs at 250 μm penetrated 2× farther into the tissue culture than MPG NPs. For all NP types, cellular internalization was severely hindered in 3D compared to monolayer.ConclusionsAlthough MPG surface modification enhances internalization and uptake in hypo-vascularized cervical tissue culture, coating with PEG reduces this internalization while enhancing penetration. A delivery strategy combining NPs with either modification may balance cellular internalization vs. tissue penetration in hypo-vascularized cervical cancer lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0185-x) contains supplementary material, which is available to authorized users.

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“…Different studies have shown that the peptides rapidly fold into predominantly helical configuration giving details on the positions of different residues [277,278]. These simulations further tell if the preferred orientation of the peptide is parallel or perpendicular to the membrane normal and if salt bridges are responsible for stabilizing this orientation [277,279].…”

Section: Computer Simulationsmentioning

confidence: 93%

Membrane Active Peptides and Their Biophysical Characterization

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Akbulut

Özkırımlı

2018

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In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide-membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

show abstract

Insights on the structural characteristics of Vim-TBS (58-81) peptide for future applications as a cell penetrating peptide

Cited by 5 publications

References 61 publications

Membrane Active Peptides and Their Biophysical Characterization

Membrane Active Peptides and Their Biophysical Characterization

Enhanced uptake and transport of PLGA-modified nanoparticles in cervical cancer

Membrane Active Peptides and Their Biophysical Characterization

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