Enhancing cellular uptake of activable cell-penetrating peptide&amp;ndash;doxorubicin conjugate by enzymatic cleavage

Shi, Nian-Qiu; Gao, Wei; Xiang, Bingren; Qi, Xian-Rong

doi:10.2147/ijn.s30104

Cited by 51 publications

(14 citation statements)

References 37 publications

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“…Cell-penetrating peptides (CPPs) are short peptides (<30 amino acids), often cationic and have the ability to internalize into the eukaryotic cells without causing significant membrane damage ( 1 – 2 ). Owing to this intrinsic cell-penetrating property, CPPs are capable of delivering conjugated therapeutic molecules like proteins ( 3 ), peptides ( 4 ), nucleic acid ( 5 – 8 ), small molecule drugs ( 9 ), nanoparticles ( 10 – 11 ), etc. to the cells and tissues.…”

Section: Introductionmentioning

confidence: 99%

CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides

et al. 2015

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CPPsite 2.0 (http://crdd.osdd.net/raghava/cppsite/) is an updated version of manually curated database (CPPsite) of cell-penetrating peptides (CPPs). The current version holds around 1850 peptide entries, which is nearly two times than the entries in the previous version. The updated data were curated from research papers and patents published in last three years. It was observed that most of the CPPs discovered/ tested, in last three years, have diverse chemical modifications (e.g. non-natural residues, linkers, lipid moieties, etc.). We have compiled this information on chemical modifications systematically in the updated version of the database. In order to understand the structure-function relationship of these peptides, we predicted tertiary structure of CPPs, possessing both modified and natural residues, using state-of-the-art techniques. CPPsite 2.0 also maintains information about model systems (in vitro/in vivo) used for CPP evaluation and different type of cargoes (e.g. nucleic acid, protein, nanoparticles, etc.) delivered by these peptides. In order to assist a wide range of users, we developed a user-friendly responsive website, with various tools, suitable for smartphone, tablet and desktop users. In conclusion, CPPsite 2.0 provides significant improvements over the previous version in terms of data content.

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Section: Introductionmentioning

confidence: 99%

CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides

et al. 2015

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“…CPPs have remarkable ability to transverse eukaryotic membranes without significant membrane damage. In addition, CPPs can carry a variety of cargoes like peptides [4,5], proteins [6], drugs [7,8], nucleic acids [9,10], siRNAs [11,12], nanoparticles [13,14], etc. across the cell membrane.…”

Section: Introductionmentioning

confidence: 99%

In silico approaches for designing highly effective cell penetrating peptides

et al. 2013

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BackgroundCell penetrating peptides have gained much recognition as a versatile transport vehicle for the intracellular delivery of wide range of cargoes (i.e. oligonucelotides, small molecules, proteins, etc.), that otherwise lack bioavailability, thus offering great potential as future therapeutics. Keeping in mind the therapeutic importance of these peptides, we have developed in silico methods for the prediction of cell penetrating peptides, which can be used for rapid screening of such peptides prior to their synthesis.MethodsIn the present study, support vector machine (SVM)-based models have been developed for predicting and designing highly effective cell penetrating peptides. Various features like amino acid composition, dipeptide composition, binary profile of patterns, and physicochemical properties have been used as input features. The main dataset used in this study consists of 708 peptides. In addition, we have identified various motifs in cell penetrating peptides, and used these motifs for developing a hybrid prediction model. Performance of our method was evaluated on an independent dataset and also compared with that of the existing methods.ResultsIn cell penetrating peptides, certain residues (e.g. Arg, Lys, Pro, Trp, Leu, and Ala) are preferred at specific locations. Thus, it was possible to discriminate cell-penetrating peptides from non-cell penetrating peptides based on amino acid composition. All models were evaluated using five-fold cross-validation technique. We have achieved a maximum accuracy of 97.40% using the hybrid model that combines motif information and binary profile of the peptides. On independent dataset, we achieved maximum accuracy of 81.31% with MCC of 0.63.ConclusionThe present study demonstrates that features like amino acid composition, binary profile of patterns and motifs, can be used to train an SVM classifier that can predict cell penetrating peptides with higher accuracy. The hybrid model described in this study achieved more accuracy than the previous methods and thus may complement the existing methods. Based on the above study, a user- friendly web server CellPPD has been developed to help the biologists, where a user can predict and design CPPs with much ease. CellPPD web server is freely accessible at http://crdd.osdd.net/raghava/cellppd/.

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“…In this regard, treatment of lung cancer cell lines positive and negative for MMP-9 demonstrated the ability of MMP-9 to significantly enhance DOX and PXL cancer cell cytotoxicity. Similar studies have shown the feasibility of this approach using an MMP-2/9 activatable DOX conjugated reagent to treat MCF-7 breast cancer cells and patient derived primary lung cancer cell lines [102,103].…”

Section: New Tools To Image Mmp Activity In Vivomentioning

confidence: 64%

New approaches to selectively target cancer-associated matrix metalloproteinase activity

Tauro

McGuire

Lynch

2014

Cancer Metastasis Rev

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Heightened matrix metalloproteinase (MMP) activity has been noted in the context of the tumor microenvironment for many years, and causal roles for MMPs have been defined across the spectrum of cancer progression. This is primarily due to the ability of the MMPs to process extracellular matrix (ECM) components and to regulate the bioavailability/activity of a large repertoire of cytokines and growth factors. These characteristics made MMPs an attractive target for therapeutic intervention but notably clinical trials performed in the 1990s did not fulfill the promise of preclinical studies. The reason for the failure of early MMP inhibitor (MMPI) clinical trials that are multifold but arguably principal among them was the inability of early MMP-based inhibitors to selectively target individual MMPs and to distinguish between MMPs and other members of the metzincin family. In the decades that have followed the MMP inhibitor trials, innovations in chemical design, antibody-based strategies, and nanotechnologies have greatly enhanced our ability to specifically target and measure the activity of MMPs. These advances provide us with the opportunity to generate new lines of highly selective MMPIs that will not only extend the overall survival of cancer patients, but will also afford us the ability to utilize heightened MMP activity in the tumor microenvironment as a means by which to deliver MMPIs or MMP activatable prodrugs.

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Enhancing cellular uptake of activable cell-penetrating peptide–doxorubicin conjugate by enzymatic cleavage

Cited by 51 publications

References 37 publications

CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides

CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides

In silico approaches for designing highly effective cell penetrating peptides

New approaches to selectively target cancer-associated matrix metalloproteinase activity

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