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Cell-penetrating peptides

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https://www.readbyqxmd.com/read/28440703/zeta-potential-changing-nanoparticles-conjugated-with-cell-penetrating-peptides-for-enhanced-transfection-efficiency
#1
Wongsakorn Suchaoin, Arshad Mahmood, Kesinee Netsomboon, Andreas Bernkop-Schnürch
AIM: The aim of this study was to develop zeta-potential-changing nanoparticles (NPs) combining cell-penetrating peptides for gene delivery. METHODS & MATERIALS: NPs were formed using phosphorylated carboxymethyl cellulose-glucosamine 6-phosphate (CMC-G6P) and polyethylene imine-polyarginine conjugates. Phosphate release was evaluated using intestinal alkaline phosphatase and cell lines. Transfection studies with plasmid DNA were then performed. RESULTS: The zeta potential of CMC-G6P/branched PEI NPs was -3 mV and switched to +4 mV after intestinal alkaline phosphatase cleavage...
April 25, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28436664/cppred-rf-a-sequence-based-predictor-for-identifying-cell-penetrating-peptides-and-their-uptake-efficiency
#2
Leyi Wei, PengWei Xing, Ran Su, Gaotao Shi, Zhanshan Sam Ma, Quan Zou
Cell-penetrating peptides (CPPs), have been proven as important drug-delivery vehicles, demonstrating the potential as therapeutic candidates. The past decade has witnessed a rapid growth in CPP-based research. Recently, many computational efforts have been made to develop machine-learning-based methods for identifying CPPs. Although much progress has been made, existing methods still suffer low feature representation capability that limits further performance improvement. In this study, we propose a novel predictor called CPPred-RF, in which we integrate multiple sequence-based feature descriptors to sufficiently explore distinct information embedded in CPPs, employ a well-established feature selection technique to improve the feature representation, and, for the first time, construct a two-layer prediction framework based on the random forest algorithm...
April 26, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28436620/arginine-rich-peptide-based-mrna-nanocomplexes-efficiently-instigate-cytotoxic-t-cell-immunity-dependent-on-the-amphipathic-organization-of-the-peptide
#3
Vimal K Udhayakumar, Ans De Beuckelaer, Joanne McCaffrey, Cian M McCrudden, Jonathan L Kirschman, Daryll Vanover, Lien Van Hoecke, Kenny Roose, Kim Deswarte, Bruno G De Geest, Stefan Lienenklaus, Philip J Santangelo, Johan Grooten, Helen O McCarthy, Stefaan De Koker
To date, the mRNA delivery field has been heavily dominated by lipid-based systems. Reports on the use of nonlipid carriers for mRNA delivery in contrast are rare in the context of mRNA vaccination. This paper describes the potential of a cell-penetrating peptide containing the amphipathic RALA motif to deliver antigen-encoding mRNA to the immune system. RALA condenses mRNA into nanocomplexes that display acidic pH-dependent membrane disruptive properties. RALA mRNA nanocomplexes enable mRNA escape from endosomes and thereby allow expression of mRNA inside the dendritic cell cytosol...
April 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28436014/a-critical-assessment-of-the-synthesis-and-biological-activity-of-p53-hdm2-stapled-peptide-inhibitors
#4
Rike Wallbrecher, Patrick Chène, Stephan Ruetz, Therese Stachyra, Thomas Vorherr, Roland Brock
BACKGROUND AND PURPOSE: Helix stapling enhances the activity of peptides that interact with a target protein in a helical conformation. These staples are also supposed to change the pharmacokinetics of the molecules and promote cytoplasmic targeting. We scrutinized to which degree the pharmacokinetic characteristics are a function of the staple and differ from those of the standard cationic cell-penetrating peptide nonaarginine for a peptide inhibiting the interaction of p53 with the human double minute 2 (Hdm2) protein...
April 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28435772/self-assembled-bifunctional-peptide-as-effective-drug-delivery-vector-with-powerful-antitumor-activity
#5
Rangrang Fan, Lan Mei, Xiang Gao, Yuelong Wang, Mingli Xiang, Yu Zheng, Aiping Tong, Xiaoning Zhang, Bo Han, Liangxue Zhou, Peng Mi, Chao You, Zhiyong Qian, Yuquan Wei, Gang Guo
E-cadherin/catenin complex is crucial for cancer cell migration and invasion. The histidine-alanine-valine (HAV) sequence has been shown to inhibit a variety of cadherin-based functions. In this study, by fusing HAV and the classical tumor-targeting Arg-Gly-Asp (RGD) motif and Asn-Gly-Arg (NGR) motif to the apoptosis-inducing peptide sequence-AVPIAQK, a bifunctional peptide has been constructed with enhanced tumor targeting and apoptosis effects. This peptide is further processed as a nanoscale vector to encapsulate the hydrophobic drug docetaxel (DOC)...
April 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28434931/effect-of-size-and-pegylation-of-liposomes-and-peptide-based-synthetic-lipoproteins-on-tumor-targeting
#6
Jie Tang, Rui Kuai, Wenmin Yuan, Lindsey Drake, James J Moon, Anna Schwendeman
Synthetic high-density lipoprotein nanoparticles (sHDL) are a valuable class of nanomedicines with established animal safety profile, clinical tolerability and therapeutic efficacy for cardiovascular applications. In this study we examined how the scavenger receptor B-I-mediated (SR-BI) tumor-targeting ability of sHDL, long plasma circulation half-life, and small particle size (9.6±0.2nm) impacted sHDL accumulation in SR-BI positive colorectal carcinoma cells, 3D tumor spheroids, and in vivo xenografts. We compared tumor accumulation of sHDL with that of liposomes (LIP, 130...
April 18, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28432017/dual-functional-nanoparticles-for-precise-drug-delivery-to-alzheimer-s-disease-lesions-targeting-mechanisms-pharmacodynamics-and-safety
#7
Xiaoyao Zheng, Chi Zhang, Qian Guo, Xu Wan, Xiayan Shao, Qingfeng Liu, Qizhi Zhang
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the cerebral accumulation of extracellular amyloid plaques. In a previous study, this histopathological hallmark was used as a target on a dual-functional nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide, a β-sheet breaker, to AD lesions precisely. This delivery system could reduce the amyloid-β (Aβ) burden in the brains of AD model mice, as well as ameliorated the memory impairment of the mice...
April 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28431917/effective-modification-of-cell-death-inducing-intracellular-peptides-by-means-of-a-photo-cleavable-peptide-array-based-screening-system
#8
Ikko Kozaki, Kazunori Shimizu, Hiroyuki Honda
Intracellular functional peptides that play a significant role inside cells have been receiving a lot of attention as regulators of cellular activity. Previously, we proposed a novel screening system for intracellular functional peptides; it combined a photo-cleavable peptide array system with cell-penetrating peptides (CPPs). Various peptides can be delivered into cells and intracellular functions of the peptides can be assayed by means of our system. The aim of the present study was to demonstrate that the proposed screening system can be used for assessing the intracellular activity of peptides...
April 18, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28431354/first-example-of-peptides-targeting-the-dimer-interface-of-leishmania-infantum-trypanothione-reductase-with-potent-in%C3%A2-vitro-antileishmanial-activity
#9
Marta Ruiz-Santaquiteria, Pedro A Sánchez-Murcia, Miguel A Toro, Héctor de Lucio, Kilian Jesús Gutiérrez, Sonia de Castro, Filipa A C Carneiro, Federico Gago, Antonio Jiménez-Ruiz, María-José Camarasa, Sonsoles Velázquez
A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem2013) has been designed and synthesized by introduction of the lactam between amino acid side chains that are separated by one helical turn (i, i+4). All of these compounds were tested in vitro as both dimerization and enzyme inhibitors of Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR in the low micromolar range and they also disrupted enzyme dimerization...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430394/structure-based-design-of-a-new-scaffold-for-cell-penetrating-peptidic-inhibitors-of-the-histone-demethylase-phf8
#10
Jerzy Dorosz, Lars Olsen, Signe Teuber Seger, Cornelia Steinhauer, Giorgos Bouras, Charlotte Helgstrand, Anders Wiuf, Michael Gajhede
The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated lysine 9 on histone H3 (H3K9me1/2) and is a transcriptional activator involved in development and cancer. Affinity and specificity of PHF8 towards H3K9me2 substrate is affected by interaction with both the catalytic domain and a PHD reader domain. The latter specifically recognizes tri-methylated lysine 4 on histone H3. A fragment of the histone H3 tail with tri-methylated lysine 4 was used as template for structure based design of a cyclic, cell-penetrating peptide that exhibits micromolar binding affinity to PHF8 in biochemical assays...
April 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28428051/cell-penetrating-peptide-cgkrk-mediates-efficient-and-widespread-targeting-of-bladder-mucosa-following-focal-injury
#11
James I Griffin, Siu Kit Kevin Cheng, Tomoko Hayashi, Dennis Carson, Manju Saraswathy, Devatha P Nair, Dmitri Simberg
The bladder presents an attractive target for topical drug delivery. The barrier function of the bladder mucosa (urothelium) presents a penetration challenge for small molecules and nanoparticles. We found that focal mechanical injury of the urothelium greatly enhances the binding and penetration of intravesically-administered cell-penetrating peptide CGKRK (Cys-Gly-Lys-Arg-Lys). Notably, the CGKRK bound to the entire urothelium, and the peptide was able to penetrate into the muscular layer. This phenomenon was not dependent on intravesical bleeding and was not caused by an inflammatory response...
April 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28421460/flow-arrest-intra-arterial-delivery-of-small-tat-decorated-and-neutral-micelles-to-gliomas
#12
Juliane Nguyen, Shaolie S Hossain, Johann R N Cooke, Jason A Ellis, Michael B Deci, Charles W Emala, Jeffrey N Bruce, Irving J Bigio, Robert M Straubinger, Shailendra Joshi
The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28420679/tumor-microenvironment-targeting-and-responsive-peptide-based-nanoformulations-for-improved-tumor-therapy
#13
Hao Qin, Yanping Ding, Ayeesha Mujeeb, Ying Zhao, Guangjun Nie
Tumor microenvironment participates in all stages of tumor progression and has emerged as a promising therapeutic target for cancer therapy. Rapid progress in the field of molecular self-assembly using various biological molecules has resulted in the fabrication of nanoformulations, specifically targeting and regulating the microenvironment components to inhibit tumor malignancies. This inhibition process is based on the differentiating biophysicochemical cues guiding tumor and normal tissue microenvironments...
April 18, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28420127/glycosaminoglycan-binding-and-non-endocytic-membrane-translocation-of-cell-permeable-octaarginine-monitored-by-real-time-in-cell-nmr-spectroscopy
#14
Yuki Takechi-Haraya, Kenzo Aki, Yumi Tohyama, Yuichi Harano, Toru Kawakami, Hiroyuki Saito, Emiko Okamura
Glycosaminoglycans (GAGs), which are covalently-linked membrane proteins at the cell surface have recently been suggested to involve in not only endocytic cellular uptake but also non-endocytic direct cell membrane translocation of arginine-rich cell-penetrating peptides (CPPs). However, in-situ comprehensive observation and the quantitative analysis of the direct membrane translocation processes are challenging, and the mechanism therefore remains still unresolved. In this work, real-time in-cell NMR spectroscopy was applied to investigate the direct membrane translocation of octaarginine (R8) into living cells...
April 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#15
Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E Nel, Huan Meng
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414223/diversity-oriented-stapling-yields-intrinsically-cell-penetrant-inducers-of-autophagy
#16
Leila Peraro, Zhongju Zou, Kamlesh M Makwana, Ashleigh Cummings, Haydn L Ball, Hongtao Yu, Yu-Shan Lin, Beth Levine, Joshua A Kritzer
Autophagy is an essential pathway by which cellular and foreign material are degraded and recycled in eukaryotic cells. Induction of autophagy is a promising approach for treating diverse human diseases, including neurodegenerative disorders and infectious diseases. Here, we report the use of a diversity-oriented stapling approach to produce autophagy-inducing peptides that are intrinsically cell-penetrant. These peptides induce autophagy at micromolar concentrations in vitro, have aggregate-clearing activity in a cellular model of Huntington's disease, and induce autophagy in vivo...
April 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28412744/mitochondrial-vdac1-based-peptides-attacking-oncogenic-properties-in-glioblastoma
#17
Anna Shteinfer-Kuzmine, Tasleem Arif, Yakov Krelin, Shambhoo Sharan Tripathi, Avijit Paul, Varda Shoshan-Barmatz
Glioblastoma multiforme (GBM), a primary brain malignancy characterized by high morbidity, invasiveness, proliferation, relapse and mortality, is resistant to chemo- and radiotherapies and lacks effective treatment. GBM tumors undergo metabolic reprograming and develop anti-apoptotic defenses. We targeted GBM with a peptide derived from the mitochondrial protein voltage-dependent anion channel 1 (VDAC1), a key component of cell energy, metabolism and apoptosis regulation. VDAC1-based cell-penetrating peptides perturbed cell energy and metabolic homeostasis and induced apoptosis in several GBM and GBM-derived stem cell lines...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412555/one-dimensional-poly-l-lysine-block-poly-l-threonine-assemblies-exhibit-potent-anticancer-activity-by-enhancing-membranolysis
#18
Yu-Fon Chen, Ai-Li Shiau, Sue-Joan Chang, Nai-Shin Fan, Chung-Teng Wang, Chao-Liang Wu, Jeng-Shiung Jan
Herein, we report the oncolytic activity of cationic, one-dimensional (1D) fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via the mitochondria-lytic effect. The concept is analogous to that of 1D drug carriers that exhibit enhanced cell penetration...
April 12, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28412450/pegylated-doxorubicin-nanoparticles-mediated-by-hn-1-peptide-for-targeted-treatment-of-oral-squamous-cell-carcinoma
#19
Yue Wang, Guoyun Wan, Zhiyuan Li, Shurui Shi, Bowei Chen, Chunyu Li, Lianyun Zhang, Yinsong Wang
HN-1, a 12-amino acid peptide, has been reported to possess strong capabilities for targeting and penetrating head and neck squamous cell carcinoma. Here, we designed a simple but effective nanoparticle system for the delivery of doxorubicin (DOX) targeting oral squamous cell carcinoma (OSCC) through the mediation of HN-1. PEGylated DOX (PD) was firstly synthesized by the conjugation of DOX with bis-amino-terminated poly(ethylene glycol) via succinyl linkage, and then PD nanoparticles were prepared by a modified nanoprecipitation method...
April 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28411183/membrane-permeation-of-arginine-rich-cell-penetrating-peptides-independent-of-transmembrane-potential-as-a-function-of-lipid-composition-and-membrane-fluidity
#20
Rike Wallbrecher, Tobias Ackels, R Alis Olea, Marco J Klein, Lucie Caillon, Jürgen Schiller, Petra H Bovée-Geurts, Toin H van Kuppevelt, Anne S Ulrich, Marc Spehr, Merel J W Adjobo-Hermans, Roland Brock
Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential...
April 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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