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Cell-penetrating peptide

Chong Chen, Kun Liu, Yupeng Xu, Pengwei Zhang, Yan Suo, Yi Lu, Wenyuan Zhang, Li Su, Qing Gu, Huamao Wang, Jianren Gu, Zonghai Li, Xun Xu
Anti-vascular endothelial growth factor (VEGF) therapies are widely used for the treatment of neovascular fundus diseases such as diabetic retinopathy. However, these agents need to be injected intravitreally, because their strong hydrophilicity and high molecular weight prevent them from penetrating cell membranes and complex tissue barriers. Moreover, the repeated injections that are required can cause infection and tissue injury. In this study, we used in vivo-directed evolution phage display technology to identify a novel dodecapeptide, named CC12, with the ability to penetrate the ocular barrier in a noninvasive (via conjunctival sac instillation) or minimally invasive (via retrobulbar injection) manner...
September 30, 2016: Biomaterials
Najla Kharrat, Sabrine Belmabrouk, Rania Abdelhedi, Riadh Benmarzoug, Mourad Assidi, Mohammed H Al Qahtani, Ahmed Rebai
BACKGROUND: The identification of charge clusters (runs of charged residues) in proteins and their mapping within the protein structure sequence is an important step toward a comprehensive analysis of how these particular motifs mediate, via electrostatic interactions, various molecular processes such as protein sorting, translocation, docking, orientation and binding to DNA and to other proteins. Few algorithms that specifically identify these charge clusters have been designed and described in the literature...
October 17, 2016: BMC Genomics
Quan Zhou, Zhao Li, Juan Zhou, Bishnu P Joshi, Gaoming Li, Xiyu Duan, Rork Kuick, Scott R Owens, Thomas D Wang
EGFR is a promising cell surface target for in vivo imaging that is highly overexpressed in hepatocellular carcinoma (HCC), a common cancer worldwide. Peptides penetrate easily into tumors for deep imaging, and clear rapidly from the circulation to minimize background. We aim to demonstrate use of an EGFR specific peptide to detect HCC xenograft tumors in mice with photoacoustic imaging. Nude mice implanted with human HCC cells that overexpress EGFR were injected intravenously with Cy5.5-labeled EGFR and scrambled control peptides respectively...
June 2016: Photoacoustics
Ying Li, Xuemin Zheng, Min Gong, Jianning Zhang
The challenge of effectively delivering therapeutic agents to the brain has created an entire field of active research devoted to overcoming the blood brain barrier (BBB) and efficiently delivering drugs to the brain. Angiopep-2 can trigger transcytosis and traverse the BBB by recognizing low-density lipoprotein related protein-1 (LRP-1) expressed on the brain capillary endothelial cells. Here, we designed a novel strategy for the delivery of drugs to the brain. The novel drug delivery system was a combination of a receptor-targeting ligand, such as low-density lipoprotein related protein 1, and a cell-penetrating peptide (CPP)...
October 17, 2016: Oncotarget
Shufang Dong, Xin Zhou, Jiying Yang
BACKGROUND: Co-delivery of anticancer drugs and gene is promising to generate synergistic anticancer effects. Surface modification of nanocarriers with specific ligands could further assist in targeting and internalization of the nanocarriers into specific cell populations, such as cancers and disease organs. PURPOSE: The aim of the study reported here is to develop Cell-penetrating peptides (CPPs) modified lipid - PEI hybrid nanoparticles (LPNs) for effective co-delivery of docetaxel (DTX) and plasmid DNA (pDNA) for combination chemotherapy...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Francis D O Ablan, B Logan Spaller, Kaitlyn I Abdo, Paulo F Almeida
Hundreds of cationic antimicrobial and cell-penetrating peptides (CPPs) form amphipathic α-helices when bound to lipid membranes. Here, we test two hypotheses for the differences in the ability of these peptides to translocate across membranes. The first, which we now call the hydrophobicity hypothesis, is that peptide translocation is determined by the Gibbs energy of insertion into the bilayer from the membrane interface. The second, which we call the charge-distribution hypothesis, is that translocation is determined by whether the distribution of cationic residues in the peptide can transiently stabilize a high-energy inserted intermediate by forming salt bridges to the phosphates of lipid headgroups...
October 18, 2016: Biophysical Journal
Yuki Daimon, Noriyasu Kamei, Kohsaku Kawakami, Mariko Takeda-Morishita, Hironori Izawa, Yuki Takechi-Haraya, Hiroyuki Saito, Hideki Sakai, Masahiko Abe, Katsuhiko Ariga
The effect of carrier morphology on the intestinal absorption of insulin was investigated using a morphology-tunable polymeric carrier, β-cyclodextrin-grafted chitosan (BCC). The insulin-BCC complexes were prepared either in acetate and citrate buffer solutions, followed by dilution with phosphate buffer for the administration. The complex had a molecular network structure in the acetate buffer, whereas nanoparticles formed in the citrate buffer. The network structure in the acetate buffer was maintained even after dilution with a phosphate buffer, but the nanoparticles in the citrate buffer caused aggregation after dilution...
October 17, 2016: Molecular Pharmaceutics
Ikuhiko Nakase, Kosuke Noguchi, Ikuo Fujii, Shiroh Futaki
Extracellular vesicles (EVs, exosomes) are approximately 30- to 200-nm-long vesicles that have received increased attention due to their role in cell-to-cell communication. Although EVs are highly anticipated to be a next-generation intracellular delivery tool because of their pharmaceutical advantages, including non-immunogenicity, their cellular uptake efficacy is low because of the repulsion of EVs and negatively charged cell membranes and size limitations in endocytosis. Here, we demonstrate a methodology for achieving enhanced cellular EV uptake using arginine-rich cell-penetrating peptides (CPPs) to induce active macropinocytosis...
October 17, 2016: Scientific Reports
Huixin Luo, Huimin Li, Xiaoyuan Yang, Jing Li, Xinge Zhang, Zhongming Wu
To overcome the chemical penetration enhancer-associated toxicities, without sacrificing delivery efficiency, a functional ε-polylysine (EPL-g-Cetyl) as polymeric permeation enhancers was synthesized by the hydrophobic modification of amino groups of ε-polylysine. The obtained EPL-g-Cetyl nanoparticles had about 200 nm in size with narrower distribution, high positive charge, and good stability. A high loading capacity (up to 17%) of the formulation provided a sustained and controlled release pattern of insulin from the nanoparticles...
October 13, 2016: Journal of Pharmaceutical Sciences
Thomas H Charpentier, Gary L Waldo, Emily G Lowery-Gionta, Krzysztof Krajewski, Brian D Strahl, Thomas L Kash, T Kendall Harden, John Sondek
In contrast to G protein-coupled receptors for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gaq binds its two major classes of effectors, the PLC-b isozymes and RhoGEFs related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gaq within its canonical binding site, consisting of a groove formed between switch II and helix a3. This information was exploited to synthesize peptides that bound active Gaq in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gaq...
October 14, 2016: Journal of Biological Chemistry
Zhao Luo, Xue-Wei Cao, Chen Li, Miao-Dan Wu, Xu-Zhong Yang, Jian Zhao, Fu-Jun Wang
Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30...
October 14, 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
Serena Marcelli, Elena Ficulle, Filomena Iannuzzi, Enikö Kövari, Robert Nisticò, Marco Feligioni
Synaptic dysfunction has been recognized as an early feature occurring at the onset of Alzheimer's disease (AD). Compromised neurotransmission leads over time to synaptic loss and these events correlate with the cognitive decline that progressively affects AD patients.Protein SUMOylation (Small Ubiquitin-like MOdifier) is a post-translational modification (PTM) involved in several cellular processes including synaptic transmission.We here demonstrate that cortical synaptosomes prepared from Tg2576 mice of 6 months of age show an increased SUMO-1ylation, which returns back to normal levels at 20 months although synaptic SUMOylation, at this age, resulted more sensible to KCl stimulus...
October 13, 2016: Molecular Neurobiology
Xinxin Gao, Karen Stanger, Harini Kaluarachchi, Till Maurer, Paulina Ciepla, Cecile Chalouni, Yvonne Franke, Rami N Hannoush
Cyclotides or cyclic cystine-knot peptides have emerged as a promising class of pharmacological ligands that modulate protein function. Interestingly, very few cyclotides have been shown to enter into cells. Yet, it remains unknown whether backbone cyclization is required for their cellular internalization. In this report, we studied the cellular behavior of EETI-II, a model acyclic cystine-knot peptide. Even though synthetic methods have been used to generate EETI-II, recombinant methods that allow efficient large scale biosynthesis of EETI-II have been lagging...
October 13, 2016: Scientific Reports
Zifan Gong, Mackenzie T Walls, Alisha N Karley, Amy J Karlsson
Cell-penetrating peptides (CPPs) are a class of small peptides that are able to cross cell membranes via direct translocation or endocytosis. They have been widely used to deliver tethered bioactive molecules to cells, but recombinantly producing CPPs as fusions to protein cargo leads to low yields. We used Escherichia coli cells to recombinantly produce genetic fusions of NPFSD (derived from a yeast endocytosis signal) and pVEC (derived from a murine vascular endothelium cadherin) to the N-terminus of green fluorescent protein (GFP) with and without a flexible glycine-serine linker between the CPP and GFP...
October 12, 2016: Molecular Biotechnology
Vedran Milosavljevic, Yazan Haddad, Miguel Angel Merlos Rodrigo, Amitava Moulick, Hana Polanska, David Hynek, Zbynek Heger, Pavel Kopel, Vojtech Adam
Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions...
2016: PloS One
Shanshan Hu, Tong Wang, Xibo Pei, He Cai, Junyu Chen, Xin Zhang, Qianbing Wan, Jian Wang
In the present study, a cell-penetrating peptide, the transactivating transcriptional factor (TAT) domain from HIV, was linked to PEGylated multi-walled carbon nanotubes (MWCNTs) to develop a highly effective antitumor drug delivery system. FITC was conjugated on MWCNTs-polyethylene glycol (PEG) and MWCNTs-PEG-TAT to provide fluorescence signal for tracing the cellular uptake of the nanocarrier. After loaded with an anticancer agent, doxorubicin (DOX) via π - π stacking interaction, the physicochemical characteristics, release profile and biological evaluation of the obtained nano-sized drug carrier were investigated...
December 2016: Nanoscale Research Letters
Xueqin Zhao, Ting Shang, Xiaodan Zhang, Ting Ye, Dajin Wang, Lei Rei
Delivery of diagnostic or therapeutic agents across the blood-brain barrier (BBB) remains a major challenge of brain disease treatment. Magnetic nanoparticles are actively being developed as drug carriers due to magnetic targeting and subsequently reduced off-target effects. In this paper, we developed a magnetic SiO2@Fe3O4 nanoparticle-based carrier bound to cell-penetrating peptide Tat (SiO2@Fe3O4(-Tat)) and studied its fates in accessing BBB. SiO2@Fe3O4-Tat nanoparticles (NPs) exhibited suitable magnetism and good biocompatibility...
December 2016: Nanoscale Research Letters
Toshihide Takeuchi, Shiroh Futaki
Arginine-rich cell-penetrating peptides (CPPs) including Tat, Penetratin and oligoarginine peptides are a series of short peptides that can be efficiently internalized into cells and have been widely used as carriers for intracellular delivery of bioactive molecules. In the early phase of the study, CPPs, as well as their conjugates, were thought to rapidly enter cells by direct penetration through membranes, which was later found to be an experimental artifact that was concluded from observations in fixed cells...
2016: Chemical & Pharmaceutical Bulletin
Martin Böhland, Eugenia Kress, Matthias B Stope, Thomas Pufe, Simone C Tauber, Lars-Ove Brandenburg
Bacterial meningitis is - despite therapeutical progress during the last decades - still characterized by high mortality and severe permanent neurogical sequelae. The brain is protected from penetrating pathogens by both the blood-brain barrier and the innate immune system. Invading pathogens are recognized by so-called pattern recognition receptors including the Toll-like receptors (TLR) which are expressed by glial immune cells in the central nervous system. Among these, TLR2 is responsible for the detection of Gram-positive bacteria such as the meningitis-causing pathogen Streptococcus pneumoniae...
October 15, 2016: Journal of Neuroimmunology
Archana Upadhya, Preeti C Sangave
Cell penetrating peptides are useful tools for intracellular delivery of nucleic acids. Delivery of plasmid DNA, a large nucleic acid, poses a challenge for peptide mediated transport. The paper investigates and compares efficacy of five novel peptide designs for complexation of plasmid DNA and subsequent delivery into cells. The peptides were designed to contain reported DNA condensing agents and basic cell penetrating sequences, octa-arginine (R8 ) and CHK6 HC coupled to cell penetration accelerating peptides such as Bax inhibitory mutant peptide (KLPVM) and a peptide derived from the Kaposi fibroblast growth factor (kFGF) membrane translocating sequence...
October 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
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