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Cell penetrating peptide

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https://www.readbyqxmd.com/read/28223245/potential-of-single-cationic-amino-acid-molecule-arginine-for-stimulating-oral-absorption-of-insulin
#1
Noriyasu Kamei, El-Sayed Khafagy, Jun Hirose, Mariko Takeda-Morishita
We have reported that cell-penetrating peptides, such as oligoarginine, act as powerful absorption enhancers for the development of oral insulin delivery systems. However, the minimal essential sequence of oligoarginine that stimulates intestinal insulin absorption remains unclear. Therefore, the present study was conducted to clarify this minimum sequence of oligoarginine and to examine the effect of single cationic amino acid arginine on the intestinal and oral absorption of insulin. The results demonstrated that a remarkable enhancement of intestinal insulin absorption was observed after coadministration of insulin with l-arginine...
February 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28213274/differentially-cleaving-peptides-as-a-strategy-for-controlled-drug-release-in-human-retinal-pigment-epithelial-cells
#2
Madhushree Bhattacharya, Sanjay Sarkhel, Jonne Peltoniemi, Robert Broadbridge, Marjo Tuomainen, Seppo Auriola, Arto Urtti
Currently, drug delivery to the posterior eye segment relies on intravitreal injections of therapeutics. This approach requires frequent injections and does not guarantee drug delivery to intracellular targets. Controlled release systems and nanoparticles are being investigated to mitigate these challenges but most of these approaches lack translational success to the clinics. In our present study, we report a peptide based delivery system that utilizes enzyme assisted cleavable linkers to release conjugated cargo within the retinal pigment epithelial (RPE) cells...
February 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28212487/interactions-between-membranes-and-metaphilic-polypeptide-architectures-with-diverse-sidechain-populations
#3
Michelle W Lee, Ming Han, Guilherme Volpe Bossa, Carly Snell, Ziyuan Song, Haoyu Tang, Lichen Yin, Jianjun Cheng, Sylvio May, Erik Luijten, Gerard C L Wong
At physiological conditions, most proteins or peptides can fold into relatively stable structures that present on their molecular surfaces specific chemical patterns partially smeared out by thermal fluctuations. These nanoscopically defined patterns of charge, hydrogen bonding, and/or hydrophobicity, along with their elasticity and shape stability (folded proteins have Young's moduli of ~1 × 10(8) Pa), largely determine and limit the interactions of these molecules, such as molecular recognition and allosteric regulation...
February 17, 2017: ACS Nano
https://www.readbyqxmd.com/read/28209404/cell-penetrating-peptides-from-basic-research-to-clinics
#4
REVIEW
Giulia Guidotti, Liliana Brambilla, Daniela Rossi
The presence of cell and tissue barriers together with the low biomembrane permeability of various therapeutics often hampers systemic drug distribution; thus, most of the available molecules are of limited therapeutic value. Opportunities to increase medicament concentrations in areas that are difficult to access now exist with the advent of cell-penetrating peptides (CPPs), which can transport into the cell a wide variety of biologically active conjugates (cargoes). Numerous preclinical evaluations with CPP-derived therapeutics have provided promising results in various disease models that, in some cases, prompted clinical trials...
February 13, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28209057/saturated-fatty-acid-analogues-of-cell-penetrating-peptide-pepfect14-role-of-fatty-acid-modification-in-complexation-and-delivery-of-splice-correcting-oligonucleotides
#5
Tõnis Lehto, Luis Vasconcelos, Helerin Margus, Ricardo Figueroa, Margus Pooga, Mattias Hällbrink, Ulo Langel
Modifying cell-penetrating peptides (CPPs) with fatty acids has long been used to improve peptide-mediated nucleic acid delivery. In this study we have revisited this phenomenon with a systematic approach where we developed a structure-activity relationship to describe the role of the acyl chain length in the transfection process. For that we took a well-studied CPP, PepFect14, as the basis and varied its N-terminal acyl chain length from 2 to 22 carbons. To evaluate the delivery efficiency, the peptides were non-covalently complexed with a splice-correcting oligonucleotide (SCO) and tested in the HeLa pLuc705 reporter cell line...
February 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28208588/depicting-binding-mediated-translocation-of-hiv-1-tat-peptides-in-living-cells-with-nanoscale-pens-of-tat-conjugated-quantum-dots
#6
Chien Y Lin, Jung Y Huang, Leu-Wei Lo
Cell-penetrating peptides (CPPs) can translocate across cell membranes, and thus have great potential for the cellular delivery of macromolecular cargoes. However, the mechanism of this cellular uptake process is not yet fully understood. In this study, a time-lapse single-particle light-sheet microscopy technique was implemented to obtain a parallel visualization of the translocating process of individual human immunodeficiency virus 1 (HIV-1) transactivator of transcription (Tat) peptide conjugated quantum dots (TatP-QDs) in complex cellular terrains...
February 10, 2017: Sensors
https://www.readbyqxmd.com/read/28205163/hybrid-in-silico-in-vitro-approaches-for-the-identification-of-functional-cholesterol-binding-domains-in-membrane-proteins
#7
Coralie Di Scala, Jacques Fantini
In eukaryotic cells, cholesterol is an important regulator of a broad range of membrane proteins, including receptors, transporters, and ion channels. Understanding how cholesterol interacts with membrane proteins is a difficult task because structural data of these proteins complexed with cholesterol are scarce. Here, we describe a dual approach based on in silico studies of protein-cholesterol interactions, combined with physico-chemical measurements of protein insertion into cholesterol-containing monolayers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28198346/characterization-of-two-new-putative-adhesins-of-leptospira-interrogans
#8
Jupciana M Figueredo, Gabriela H Siqueira, Gisele O de Souza, Marcos B Heinemann, Silvio A Vasconcellos, Erica G B Chapola, Ana L T O Nascimento
We here report the characterization of two novel proteins encoded by the genes LIC11122 and LIC12287, identified in the genome sequences of Leptospira interrogans, annotated, respectively, as a putative sigma factor and a hypothetical protein. The CDSs LIC11122 and LIC12287 have signal peptide SPII and SPI and are predicted to be located mainly at the cytoplasmic membrane of the bacteria. The genes were cloned and the proteins expressed using Escherichia coli. Proteinase K digestion showed that both proteins are surface exposed...
January 2017: Microbiology
https://www.readbyqxmd.com/read/28195491/prodrug-like-pegylated-protein-toxin-trichosanthin-for-reversal-of-chemoresistance
#9
Yingzhi Chen, Meng Zhang, Hongyue Jin, Yisi Tang, Aihua Wu, Qin Xu, Yongzhuo Huang
Multidrug resistance (MDR) is a main obstacle in cancer chemotherapy. The MDR mechanisms involve P-glycoprotein (P-gp) overexpression, abnormality of apoptosis-related protein, and altered expression of drug-targeting proteins. Therapeutic proteins are emerging as candidates for overcoming cancer MDR because of not only their large molecular size that potentially circumvents the P-gp-mediated drug efflux but also their distinctive bioactivity distinguished from small-molecular drugs. Herein we report trichosanthin, a plant protein toxin, possesses synergistic effect with paclitaxel (PTX) in the PTX-resistance A549/T nonsmall cell lung cancer (NSCLC) cells, by reversing PTX-caused caspase 9 phosphorylation and inducing caspase 3-dependent apoptosis...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28194980/cell-penetrating-peptide-spirolactam-derivative-as-a-reversible-fluorescent-ph-probe-for-live-cell-imaging
#10
Meng-Chan Xia, Lesi Cai, Sichun Zhang, Xinrong Zhang
A colorless and nonfluorescent spirolactam derivative, RhB-R12K, was synthesized by amide condensation between the carboxyl group of rhodamine B (RhB) and the amino group of cell-penetrating peptide (CPP). The fluorescence intensity of RhB-R12K sharply increased as the pH value decreased from 8.0 to 4.9, demonstrating sensitive and reversible response to intracellular pH distribution. This CPP probe was completely water soluble, had low cytotoxicity, was membrane permeable, and was suitable for pH measurement in various organelles by choosing organelle-specific CPP sequences...
January 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28194967/multicellular-tumor-spheroids-combined-with-mass-spectrometric-histone-analysis-to-evaluate-epigenetic-drugs
#11
Peter E Feist, Simone Sidoli, Xin Liu, Monica M Schroll, Sharif Rahmy, Rina Fujiwara, Benjamin A Garcia, Amanda B Hummon
Multicellular tumor spheroids (MCTS) are valuable in vitro tumor models frequently used to evaluate the penetration and efficacy of therapeutics. In this study, we evaluated potential differences in epigenetic markers, i.e., histone post-translational modifications (PTMs), in the layers of the HCT116 colon carcinoma MCTS. Cells were grown in agarose-coated 96 well plates, forming reproducible 1-mm-diameter MCTS. The MCTS were fractionated into three radially concentric portions, generating samples containing cells from the core, the mid and the external layers...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28194842/infectivity-inhibition-by-overlapping-synthetic-peptides-derived-from-the-gh-gl-heterodimer-of-herpes-simplex-virus-type-1
#12
Gianluigi Franci, Annarita Falanga, Carla Zannella, Veronica Folliero, Francesca Martora, Marilena Galdiero, Stefania Galdiero, Giancarlo Morelli, Massimiliano Galdiero
Herpes simplex virus (HSV) is a human pathogen that infects epithelial cells. The cutaneous lesions, caused by the virus, spread to the nervous system creating several complications. Fusion of host membranes with the viral envelope is mandatory and mediated by a group of glycoproteins conserved in all Herpesviridae subfamilies, such as the glycoproteins B (gB), H (gH), L (gL) and D (gD). We investigated the inhibitory activity mediated by synthetic overlapping peptides spanning the entire ectodomains of gH and gL glycoproteins...
February 14, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28193017/single-particle-tracking-of-peptides-modified-nanocargo-on-lipid-membrane-revealing-bulk-mediated-diffusion
#13
Lin Wei, Zhongju Ye, Yueling Xu, Bo Chen, Edward S Yeung, Lehui Xiao
Understanding the detailed diffusion behavior of the nanocargo on lipid membrane can afford deep insight into the surface chemistry controlled translocation mechanism for the rational design of an efficient delivery system. By tracking the diffusion trajectory of transacting activator of transcription (TAT, a cell penetrating peptide) peptides-modified nanocargo on lipid membrane, bulk-mediated (intermittent hopping) diffusion was observed for the first time after a blended modification of TAT peptides and polyethylene glycol (PEG) molecules onto the nanoparticle surface...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28192531/multi-layered-control-of-galectin-8-mediated-autophagy-during-adenovirus-cell-entry-through-a-conserved-ppxy-motif-in-the-viral-capsid
#14
Charlotte Montespan, Shauna A Marvin, Sisley Austin, Andrew M Burrage, Benoit Roger, Fabienne Rayne, Muriel Faure, Edward M Campell, Carola Schneider, Rudolph Reimer, Kay Grünewald, Christopher M Wiethoff, Harald Wodrich
Cells employ active measures to restrict infection by pathogens, even prior to responses from the innate and humoral immune defenses. In this context selective autophagy is activated upon pathogen induced membrane rupture to sequester and deliver membrane fragments and their pathogen contents for lysosomal degradation. Adenoviruses, which breach the endosome upon entry, escape this fate by penetrating into the cytosol prior to autophagosome sequestration of the ruptured endosome. We show that virus induced membrane damage is recognized through Galectin-8 and sequesters the autophagy receptors NDP52 and p62...
February 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28190655/development-of-helix-stabilized-cell-penetrating-peptides-containing-cationic-%C3%AE-%C3%AE-disubstituted-amino-acids-as-helical-promoters
#15
Hiroko Yamashita, Takashi Misawa, Makoto Oba, Masakazu Tanaka, Mikihiko Naito, Masaaki Kurihara, Yosuke Demizu
Cell-penetrating peptides (CPP) have attracted many scientists' attention as intracellular delivery tools due to their high cargo molecule transportation efficiency and low cytotoxicity. Therefore, in many research fields CPP, such as HIV-Tat and oligoarginine (Rn), are used to deliver hydrophilic drugs and biomolecules, including proteins, DNA, and RNA. We designed four types of CPP that contained cationic α,α-disubstituted amino acids (Api(C2Gu) and Api(C4Gu)) as helical promoters; i.e., 1-4 [FAM-β-Ala-(l-Arg-l-Arg-Xaa)3-(Gly)3-NH2 (1: Xaa=Api(C2Gu), 2: Xaa=Api(C4Gu)), 3: FAM-β-Ala-(l-Arg)8-Api(C2Gu)-(Gly)3-NH2, and 4: FAM-β-Ala-(l-Arg)5-Api(C2Gu)-(l-Arg)2-Api(C2Gu)-(Gly)3-NH2], and investigated their preferred secondary structures and cell membrane-penetrating ability...
February 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28185449/positively-charged-combinatory-drug-delivery-systems-against-multi-drug-resistant-breast-cancer-beyond-the-drug-combination
#16
Xu Yan, Qingsong Yu, Linyi Guo, Wenxuan Guo, Shuli Guan, Hao Tang, Shanshan Lin, Zhihua Gan
The formation and development of cancer is usually accompanied by angiogenesis and is related to multiple pathways. The inhibition of one pathway by monotherapy might result in the occurrence of drug resistance, tumor relapse, or metastasis. Thus, a combinatory therapeutic system that targets several independent pathways simultaneously is preferred for the treatment. To this end, we prepared combinatory drug delivery systems consisting of cytotoxic drug SN38, pro-apoptotic KLAK peptide, and survivin siRNA with high drug loading capacity and reductive responsiveness for the treatment of multi-drug-resistant (MDR) cancer...
February 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28183803/hexokinase-ii-derived-cell-penetrating-peptide-targets-mitochondria-and-triggers-apoptosis-in-cancer-cells
#17
Abiy D Woldetsadik, Maria C Vogel, Wael M Rabeh, Mazin Magzoub
Overexpression of mitochondria-bound hexokinase II (HKII) in cancer cells plays an important role in their metabolic reprogramming and protects them against apoptosis, thereby facilitating their growth and proliferation. Here, we show that covalently coupling a peptide that corresponds to the mitochondrial membrane-binding N-terminal domain of HKII (pHK) to a short, penetration-accelerating sequence (PAS) enhances the cellular uptake, mitochondrial localization, and cytotoxicity of the peptide in HeLa cells...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28182666/direct-protein-introduction-into-plant-cells-using-a-multi-gas-plasma-jet
#18
Yuki Yanagawa, Hiroaki Kawano, Tomohiro Kobayashi, Hidekazu Miyahara, Akitoshi Okino, Ichiro Mitsuhara
Protein introduction into cells is more difficult in plants than in mammalian cells, although it was reported that protein introduction was successful in shoot apical meristem and leaves only together with a cell-penetrating peptide. In this study, we tried to introduce superfolder green fluorescent protein (sGFP)-fused to adenylate cyclase as a reporter protein without a cell-penetrating peptide into the cells of tobacco leaves by treatment with atmospheric non-thermal plasmas. For this purpose, CO2 or N2 plasma was generated using a multi-gas plasma jet...
2017: PloS One
https://www.readbyqxmd.com/read/28178415/tumor-penetrating-nanosystem-strongly-suppresses-breast-tumor-growth
#19
Shweta Sharma, Venkata Ramana Kotamraju, Tarmo Molder, Allan Tobi, Tambet Teesalu, Erkki Ruoslahti
Antiangiogenic and vascular disrupting compounds have shown promise in cancer therapy, but tend to be only partially effective. We previously reported a potent theranostic nanosystem that was highly effective in glioblastoma and breast cancer mouse models, retarding tumor growth and producing some cures [Agemy et al. 2011,2013]. The nanosystem consists of iron oxide NPs ("nanoworms") coated with a composite peptide with tumor-homing and pro-apoptotic domains. The homing component targets tumor vessels by binding to p32/gC1qR at the surface or tumor endothelial cells...
February 8, 2017: Nano Letters
https://www.readbyqxmd.com/read/28178347/mitochondria-penetrating-peptides-conjugated-to-desferrioxamine-as-chelators-for-mitochondrial-labile-iron
#20
Roxana Y P Alta, Hector A Vitorino, Dibakar Goswami, Cleber W Liria, Simon P Wisnovsky, Shana O Kelley, M Terêsa Machini, Breno P Espósito
Desferrioxamine (DFO) is a bacterial siderophore with a high affinity for iron, but low cell penetration. As part of our ongoing project focused on DFO-conjugates, we synthesized, purified, characterized and studied new mtDFOs (DFO conjugated to the Mitochondria Penetrating Peptides TAT49-57, 1A, SS02 and SS20) using a succinic linker. These new conjugates retained their strong iron binding ability and antioxidant capacity. They were relatively non toxic to A2780 cells (IC50 40-100 μM) and had good mitochondrial localization (Rr +0...
2017: PloS One
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