CPPsite: a curated database of cell penetrating peptides

Gautam, Ankur; Singh, Harinder; Tyagi, Atul; Chaudhary, Kumardeep; Kumar, Rahul; Kapoor, Pallavi; Raghava, Gajendra P. S.

doi:10.1093/database/bas015

Cited by 172 publications

(171 citation statements)

References 24 publications

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“…Cell-penetrating peptides (CPPs) are capable of mediating penetration of the plasma membrane, allowing delivery of macromolecular cargos to which they are attached to cell interiors. CPPs are typically 10-30 amino acids long and fall into one of three major categories: arginine-rich, amphipathic and lysine-rich, and hydrophobic (Gautam et al, 2012). CPP delivery of cargos to the interior compartments of cells is potentially transformative as a research tool, diagnostic aid and therapeutic mechanism.…”

Section: Introductionmentioning

confidence: 99%

Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos

Salerno

Ngwa

Nowak

et al. 2016

Journal of Cell Science

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Fig. 2. Confocal imaging of cell penetration. BHK cells were treated for 1 h with DyLight 550 fluorescently labeled cargo proteins β-Gal (A), HRP (B) and myoglobin (C) (rendered as white in left panels, red in center and right panels), in either the absence or presence of TAT-CaM, washed and imaged live. Center images are optical sections set at a similar depth of the nucleus (NucBlue staining, white, center and right panels), as determined by position within the Z-stack. Orthogonal projections are shown at the right (boxed in red) and top (boxed in green) sides of each panel. Cytoplasmic compartments in live cells were visualized using CellTracker Green CMFDA dye (green in right panels). Comparison of TAT-CaM-treated versus untreated cells indicates that cargo proteins are entering the cell, and are localized primarily to the cytoplasm. Scale bars in all panels, 20 μm. Each experiment was replicated at least twice with the same results. 2474 ABSTRACTThe use of cell-penetrating peptides (CPPs) as biomolecular delivery vehicles holds great promise for therapeutic and other applications, but development has been stymied by poor delivery and lack of endosomal escape. We have developed a CPP-adaptor system capable of efficient intracellular delivery and endosomal escape of user-defined protein cargos. The cell-penetrating sequence of HIV transactivator of transcription was fused to calmodulin, which binds with subnanomolar affinity to proteins containing a calmodulin binding site. Our strategy has tremendous advantage over prior CPP technologies because it utilizes high-affinity non-covalent, but reversible coupling between CPP and cargo. Three different cargo proteins fused to a calmodulin binding sequence were delivered to the cytoplasm of eukaryotic cells and released, demonstrating the feasibility of numerous applications in living cells including alteration of signaling pathways and gene expression.

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Section: Introductionmentioning

confidence: 99%

Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos

Salerno

Ngwa

Nowak

et al. 2016

Journal of Cell Science

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“…1C), can be assigned to two distinct CPP families [4,5,7]: pepM is highly hydrophobic and contains two Pro residues, which is typical of the hydrophobic/Pro CPP family, and pepR is highly cationic (+12) and fits the requirements of the Arg/Lys-rich CPP family [4,5,7]. MCPEP, a computational tool that estimates the probability of occurrence of secondary structure in peptides (both in aqueous environment and when inserted in lipid bilayers) by Monte Carlo simulation [22], predicts that both peptides acquire a random coil conformation in water.…”

Section: Resultsmentioning

confidence: 99%

“…The two CPPs have different biochemical properties and may be considered new members of two different CPP classes [4,5,7]: Arg-rich CPP (pepR) and hydrophobic Pro-rich CPP (pepM). Our study reinforces the idea that the former uses endocytic and the latter nonendocytic mechanisms, thus supporting the view that CPP internalization routes are class-dependent [4].…”

Section: Discussionmentioning

confidence: 99%

“…small RNA/DNA, plasmids, antibodies and nanoparticles). Typically, CPPs contain 6-30 amino acid residues, ranging from highly charged (Arg-and Lys-rich sequences) to hydrophobic or amphipathic [4][5][6][7] sequences, easily amenable to molecular tuning to achieve high internalization yields [8][9][10]. Their use in biomedical applications has been extensively evaluated [3,5,11], with a strong focus on their ability to deliver small interfering RNA (siRNA), genes and plasmids of pharmaceutical interest [5,[11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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Cell penetrating peptides (CPPs) can be used as drug delivery systems for different therapeutic molecules. In this work two novel CPPs, pepR and pepM, designed from two domains of the dengue virus (DENV) capsid protein, were studied for their ability to deliver nucleic acids into cells as non-covalently bound cargo. Translocation studies were performed by confocal microscopy in HepG2, BHK and HEK cell lineages, astrocytes and peripheral blood mononuclear cells. Combined studies in HepG2 cells, astrocytes and BHK cells, at 4 and 37°C or using specific endocytosis inhibitors, revealed that pepR and pepM use distinct internalization routes: pepM translocates lipid membranes directly, while pepR uses an endocytic pathway. To confirm these results, a methodology was developed to monitor the translocation kinetics of both peptides by real-time flow cytometry. Kinetic constants were determined, and the amount of nucleic acids delivered was estimated. Additional studies were performed in order to understand the molecular bases of the peptide-mediated translocation. Peptide-nucleic acid and peptide-lipid membrane interactions were studied quantitatively based on the intrinsic fluorescence of the peptides. pepR and pepM bound ssDNA to the same extent. Partition studies revealed that both peptides bind preferentially to anionic lipid membranes, adopting an a-helical conformation. However, fluorescence quenching studies suggest that pepM is deeply inserted into the lipid bilayer, in contrast with pepR. Moreover, only pepM is able to promote the fusion and aggregation of vesicles composed of zwitterionic lipids. Altogether, the results show that DENV capsid protein derived peptides serve as good templates for novel CPP-based nucleic acid delivery strategies, defining different routes for cell entry.

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“…These peptides have a helical secondary structure with the hydrophobic and hydrophilic domains. They use the charged region for cell membrane interaction and the hydrophobic region for membrane perturbation and translocation [29,39]. Moreover, several studies have shown that the presence of tryptophan and backbone spacing can affect the uptake efficiency as well as its mechanism [40].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

Mohammadi

Zakeri–Milani

Golkar

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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A new class of cell penetrating peptides (CPPs) named peptide amphiphile was designed to improve the intracellular uptake and antitumor activity of epirubicin (EPR). Various amphiphilic CPPs were synthesized by solid phase peptide synthesis method and were chemically conjugated to EPR. Their corresponding nanoparticles (CPPs-E4 and CPPs-E8)were prepared via non-covalent binding of the peptides and polyanions. Cytotoxicity and anti-proliferative activity were evaluated by MTT assay. Cellular uptake was examined by flow cytometry and fluorescence microscopy. The CPPs exhibited slight cytotoxicity.Binding of polyglutamate to CPPs (CPPs-E4 and CPPs-E8 nanoparticles) decreased their cytotoxicity. CPPs-E8 nanoparticles showed lower cytotoxicity than CPPs-E4 nanoparticles.Cellular uptake of K3W4K3-E8, K2W4K2-E8 and W3K4W3-E8 reached 100% with no difference between each of the mentioned CPPs and its nanoparticle at 50 µM. The antiproliferative activity of EPR was enhanced following conjugation to peptides and nanoparticles at 25 µM. CPPs-EPR-E4 and -E8 nanoparticles displayed higher antiproliferative activity than CPPs-EPR at 25 µM. CPPs-E8-EPR nanoparticles showed higher anti-proliferative activity than CPPs-E4-EPR. K3W4K3-E8-EPR nanoparticles exhibited the highest anti-proliferative activity at 25 µM. The synthesized peptide nanoparticles are proposed as suitable carriers for improving the intracellular delivery of EPR into tumor cells with low cytotoxicity and high antitumor activity.

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CPPsite: a curated database of cell penetrating peptides

Cited by 172 publications

References 24 publications

Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos

Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos

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

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

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