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Cell-penetrating peptide

Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Caroline K Søgaard, Siver A Moestue, Morten B Rye, Jana Kim, Anala Nepal, Nina-Beate Liabakk, Siri Bachke, Tone F Bathen, Marit Otterlei, Deborah K Hill
Docetaxel is the chemotherapeutic choice for metastatic hormone-refractory prostate cancer, however, it only marginally improves the survival rate. The purpose of the present study was to examine if a peptide targeting the cellular scaffold protein PCNA could improve docetaxel's efficacy. We found that docetaxel given in combination with a cell penetrating peptide containing the AlkB homolog 2 PCNA interacting motif (APIM-peptide), reduced the prostate volume and limited prostate cancer regrowth in vivo in the immunocompetent transgenic adenocarcinoma model of prostate cancer (TRAMP)...
February 20, 2018: Oncotarget
Emily Wonder, Lorena Simón-Gracia, Pablo Scodeller, Ramsey N Majzoub, Venkata Ramana Kotamraju, Kai K Ewert, Tambet Teesalu, Cyrus R Safinya
Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells...
March 2, 2018: Biomaterials
Xiubao Chang, Yuexian Hou
Genome editing is a powerful tool to modify a specific gene and to correct a disease-causing mutation. Recently developed new techniques, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9), significantly facilitate the progression in this field. However, mutations associated with the double strand DNA breaks (DSBs) introduced by these systems hampered their direct usage in clinic. In order to prevent the mutations caused by DSBs, we have designed a novel mean to induce homology-directed recombination (HDR) without DSBs, i...
2018: International Journal of Biochemistry and Molecular Biology
Shota Ichimizu, Hiroshi Watanabe, Hitoshi Maeda, Keisuke Hamasaki, Yuka Nakamura, Victor Tuan Giam Chuang, Ryo Kinoshita, Kento Nishida, Ryota Tanaka, Yuki Enoki, Yu Ishima, Akihiko Kuniyasu, Yoshihiro Kobashigawa, Hiroshi Morioka, Shiro Futaki, Masaki Otagiri, Toru Maruyama
Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA...
March 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Katia Pane, Mariavittoria Verrillo, Angela Avitabile, Elio Pizzo, Mario Varcamonti, Anna Zanfardino, Antimo Di Maro, Camilla Rega, Angela Amoresano, Viviana Izzo, Alberto Di Donato, Valeria Cafaro, Eugenio Notomista
Peptides with an N-terminal cysteine residue allow site-specific modification of proteins and peptides and chemical synthesis of proteins. They have been widely used to develop new strategies for imaging, drug discovery, diagnostics and chip technologies. Here we present a method to produce recombinant peptides with an N-terminal cysteine residue as a convenient alternative to chemical synthesis. The method is based on the release of the desired peptide from a recombinant fusion protein by mild acid hydrolysis of an Asp-Cys sequence...
March 12, 2018: Bioconjugate Chemistry
Rui Huang, Jiawei Li, Dereje Kebebe, Yumei Wu, Bing Zhang, Zhidong Liu
Tumor-targeted delivery is considered a crucial component of current anticancer drug development and is the best approach to increase the efficacy and reduce the toxicity. Nanomedicine, particularly ligand-based nanoparticles have shown a great potential for active targeting of tumor. Cell penetrating peptide is one of the promising ligands in a targeted cancer therapy. In this study, the gambogic acid-loaded nanostructured lipid carrier (GA-NLC) was modified with two kinds of cell penetrating peptides (cRGD and RGERPPR)...
November 2018: Drug Delivery
Md Zahidul Islam, Sabrina Sharmin, Md Moniruzzaman, Masahito Yamazaki
Cell-penetrating peptides (CPPs) can translocate across the plasma membrane of living eukaryotic cells and enter the cytosol without significantly affecting cell viability. Consequently, CPPs have been used for the intracellular delivery of biological cargo such as proteins and oligonucleotides. However, the mechanisms underlying the translocation of CPPs across the plasma membrane remain unclear. In this mini-review, we summarize the experimental results regarding the entry of CPPs into lipid bilayer vesicles obtained using three methods: the large unilamellar vesicle (LUV) suspension method, the giant unilamellar vesicle (GUV) suspension method, and the single GUV method...
March 9, 2018: Applied Microbiology and Biotechnology
Alphonse Garcia
Small viral proteins with cationic domains can be involved in multiple biological processes including cell penetration or interaction with intracellular targets. Within the last two decades several reports indicated that the C-terminus of HIV-1 Vpr is a cell penetrating sequence, a PP2A-dependent death domain and also displays toxicity against Gram-negative E. coli. Interestingly, HIV-1 Vpr, as well as some cationic proteins encoded by different viruses, share similar physical properties with the unique anti-microbial human cathelicidin LL37 peptide...
April 2018: Medical Hypotheses
Zhigao Niu, Eleni Samaridou, Emilie Jaumain, Julie Coëne, Gabriela Ullio, Neha Shrestha, Josep Garcia, Matilde Durán-Lobato, Sulay Tovar, Manuel J Santander-Ortega, M Victoria Lozano, M Mar Arroyo-Jiménez, Rocío Ramos-Membrive, Iván Peñuelas, Aloïse Mabondzo, Véronique Préat, Meritxell Teixidó, Ernest Giralt, María José Alonso
The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a nanocomplex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer...
March 5, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ja-Hyun Koo, Heeseok Yoon, Won-Ju Kim, Donghun Cha, Je-Min Choi
Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates cellular responses such as proteasomal degradation and DNA repair upon interaction with its substrate. We identified a highly cationic region within the PAR-binding motif of Iduna; the region was similar among various species and showed amino acid sequence similarity with that of known cell-penetrating peptides (CPPs). We hypothesized that this Iduna-derived cationic sequence-rich peptide (Iduna) could penetrate the cell membrane and deliver macromolecules into cells...
March 8, 2018: International Journal of Molecular Sciences
Céléna Dubuc, Martin Savard, Veronica Bovenzi, Andrée Lessard, Audrey Fortier, Jérôme Côté, Witold Neugebauer, Flavio Rizzolio, Sameh Geha, Antonio Giordano, Sylvain Chemtob, Fernand Gobeil
G protein-coupled receptors (GPCRs) are integral cell-surface proteins having a central role in tumor growth and metastasis. However, several GPCRs retain an atypical intracellular/nuclear location in various types of cancer. The pathological significance of this is currently unknown. Here we extend this observation by showing that the bradykinin B2R (BK-B2R) is nuclearly expressed in the human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and in human clinical specimens of TNBC. We posited that these "nuclearized" receptors could be involved in oncogenic signaling linked to aberrant growth and survival maintenance of TNBC...
February 9, 2018: Oncotarget
Leyi Wei, Jijun Tang, Quan Zou
BACKGROUND: Cell-penetrating peptides (CPPs) are short peptides (5-30 amino acids) that can enter almost any cell without significant damage. On account of their high delivery efficiency, CPPs are promising candidates for gene therapy and cancer treatment. Accordingly, techniques that correctly predict CPPs are anticipated to accelerate CPP applications in future therapeutics. Recently, computational methods have been reportedly successful in predicting CPPs. Unfortunately, the predictive performance of existing methods is not satisfactory and reliable so as to accurately identify CPPs...
October 16, 2017: BMC Genomics
Ruchi Omar, Arpita Yadav
In this opinion article, the authors discuss a number of interesting, beneficial properties of naturally occurring and synthetic cationic antimicrobial peptides (AMPs) with the prospective aim of bringing these compounds into therapeutic use to avoid antibiotic resistance and utilize their numerous properties. The structural diversity and the conformational freedom of these compounds adversely affects their mechanistic elucidation. Our molecular level mechanistic exploration of these peptides has shown their ion carriage properties and systematically explains their antibiotic activity through disruption of bacterial cell homeostasis and inhibition of 14-α demethylase enzyme...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Annely Lorents, Pille Säälik, Ulo Langel, Margus Pooga
Proficient transport vectors called cell-penetrating peptides (CPPs) internalize into eukaryotic cells mostly via endocytic pathways and facilitate the uptake of various cargo molecules attached to them. However, some CPPs are able to induce disturbances in the plasma membrane and translocate through it seemingly in energy-independent manner. For understanding this phenomenon, giant plasma membrane vesicles (GPMVs) derived from the cells is a beneficial model system, since GPMVs have a complex membrane composition comparable to the cells, yet lack cellular energy-dependent mechanisms...
March 6, 2018: Bioconjugate Chemistry
Morgan Grau, Paul R Walker, Madiha Derouazi
Immunotherapies are increasingly used to treat cancer, with some outstanding results. Immunotherapy modalities include therapeutic vaccination to eliminate cancer cells through the activation of patient's immune system against tumor-derived antigens. Nevertheless, the full potential of therapeutic vaccination has yet to be demonstrated clinically because many early generation vaccines elicited low-level immune responses targeting only few tumor antigens. Cell penetrating peptides (CPPs) are highly promising tools to advance the field towards clinical success...
March 5, 2018: Cellular and Molecular Life Sciences: CMLS
Jiawei Wu, Yaxian Zheng, Min Liu, Wei Shan, Zhirong Zhang, Yuan Huang
Nanoparticles (NPs) for oral delivery of peptide/protein drugs are largely limited due to the co-existence of intestinal mucus and epithelial barriers. Sequentially overcoming these two barriers is intractable to realize in single nanovehicle because it needs different or even contradictory surface properties of NPs. To solve this dilemma, a biomimetic mucus penetrating virus-inspired NPs meanwhile with charge reversal ability (P-R8-Pho NPs) were developed by densely coating PLGA NPs with cationic octa-arginine (R8) peptide and specific anionic phosphoserine (Pho)...
March 5, 2018: ACS Applied Materials & Interfaces
N Ashwanikumar, Justin S Plaut, Barmak Mostofian, Siddharth Patel, Peter Kwak, Conroy Sun, Kerry McPhail, Daniel M Zuckerman, Sadik C Esener, Gaurav Sahay
Despite recent advances in the supramolecular assembly of cell-penetrating peptide (CPP) nanostructures, the tuning of size, shape, morphology and packaging of drugs in these materials still remain unexplored. Herein, through sequential ligation of peptide building blocks, we create cell-penetrating self-assembling peptide nanomaterials (CSPNs) with the capability to translocate inside cells. We devised a triblock array of Tat48-59 [HIV-1 derived transactivator of transcription48-59 ] based CPPs, conjugated to up to four Phenylalanine (Phe) residues through an amphiphilic linker, (RADA)2 ...
March 1, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jlenia Brunetti, Giulia Riolo, Mariangela Gentile, Andrea Bernini, Eugenio Paccagnini, Chiara Falciani, Luisa Lozzi, Silvia Scali, Lorenzo Depau, Alessandro Pini, Pietro Lupetti, Luisa Bracci
BACKGROUND: Near-infrared quantum dots (NIR QDs) are a new class of fluorescent labels with excellent bioimaging features, such as high fluorescence intensity, good fluorescence stability, sufficient electron density, and strong tissue-penetrating ability. For all such features, NIR QDs have great potential for early cancer diagnosis, in vivo tumor imaging and high resolution electron microscopy studies on cancer cells. RESULTS: In the present study we constructed NIR QDs functionalized with the NT4 cancer-selective tetrabranched peptides (NT4-QDs)...
March 3, 2018: Journal of Nanobiotechnology
Krista Freimann, Piret Arukuusk, Kaido Kurrikoff, Ly Pärnaste, Raivo Raid, Andres Piirsoo, Margus Pooga, Ülo Langel
Although advances in genomics and experimental gene therapy have opened new possibilities for treating otherwise incurable diseases, the transduction of nucleic acids into the cells and delivery in vivo remain challenging. The high molecular weight and anionic nature of nucleic acids require their packing into nanoparticles for the delivery. The efficacy of nanoparticle drugs necessitates the high bioactivity of constituents, but their distribution in organisms is mostly governed by the physical properties of nanoparticles, and therefore, generation of stable particles with strictly defined characteristics is highly essential...
March 2, 2018: Molecular Therapy. Nucleic Acids
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