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Cell-penetrating peptide

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https://www.readbyqxmd.com/read/28634358/hiv-1-gp41-targeting-fusion-inhibitory-peptides-enhance-the-gp120-targeting-protein-mediated-inactivation-of-hiv-1-virions
#1
Qianqian Qi, Qian Wang, Weizao Chen, Lanying Du, Dimiter S Dimitrov, Lu Lu, Shibo Jiang
Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT)...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28634138/intracellular-and-transdermal-protein-delivery-mediated-by-non-covalent-interactions-with-a-synthetic-guanidine-rich-molecular-carrier
#2
Jungkyun Im, Sanket Das, Dongjun Jeong, Chang-Jin Kim, Hyun-Suk Lim, Ki Hean Kim, Sung-Kee Chung
The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins...
June 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28631963/tumor-penetrating-peptide-integrated-thermally-sensitive-liposomal-doxorubicin-enhances-efficacy-of-radiofrequency-ablation-in-liver-tumors
#3
Fei Yan, Song Wang, Wei Yang, S Nahum Goldberg, Hao Wu, Wan-Lu Duan, Zhi-Ting Deng, Hai-Bo Han, Hai-Rong Zheng
Purpose To investigate the role of a tumor-penetrating peptide (internalizing CRGDRGPDC [iRGD])-integrated thermally sensitive liposomal (TSL) doxorubicin (DOX) in combination with radiofrequency (RF) ablation of liver tumors in an animal model. Materials and Methods Approval from the institutional animal care and use committee was obtained. Characterization of iRGD-TSL-DOX was performed in vitro. Next, H22 liver adenocarcinomas were implanted in 138 mice in vivo. The DOX accumulation and cell apoptosis of iRGD-TSL-DOX and TSL-DOX with or without RF were evaluated (n = 5) at different time points after treatment with quantitative analysis or pathologic staining...
June 19, 2017: Radiology
https://www.readbyqxmd.com/read/28629518/analysis-of-the-asymmetry-of-activated-epo-receptor-enables-designing-small-molecule-agonists
#4
Frank Guarnieri
Amgen solved the high-resolution cocrystal structure of erythropoietin (EPO) bound to the extracellular part of the receptor (EPOR) in 1998, which reveals that the EPO-EPOR interaction surface is formed by 11 salt bridges, 17 H-bonds, and 2 hydrophobic clusters centered at a pair of crucial phenylalanines (F93). The EPOR has two domains, one that penetrates the membrane and a second extracellular domain that forms one arm of the binding site for the EPO ligand. The complete competent receptor-binding site is a homodimer of EPOR with the two arms forming a funnel-shaped cup where EPO binds...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28626568/dual-targeted-peptide-conjugated-multifunctional-fluorescent-probe-with-aiegen-for-efficient-nucleus-specific-imaging-and-long-term-tracing-of-cancer-cells
#5
Yong Cheng, Chunli Sun, Xiaowen Ou, Bifeng Liu, Xiaoding Lou, Fan Xia
Precisely targeted transportation of a long-term tracing regent to a nucleus with low toxicity is one of the most challenging concerns in revealing cancer cell behaviors. Here, we report a dual-targeted peptide-conjugated multifunctional fluorescent probe (cNGR-CPP-NLS-RGD-PyTPE, TCNTP) with aggregation-induced emission (AIE) characteristic, for efficient nucleus-specific imaging and long-term and low-toxicity tracing of cancer cells. TCNTP mainly consists of two components: one is a functionalized combinatorial peptide (TCNT) containing two targeted peptides (cNGR and RGD), a cell-penetrating peptide (CPP) and a nuclear localization signal (NLS), which can specifically bind to a cell surface and effectively enter into the nucleus; the other one is an AIE-active tetraphenylethene derivative (PyTPE, a typical AIEgen) as fluorescence imaging reagent...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28624185/the-formation-of-nanoparticles-between-small-interfering-rna-and-amphipathic-cell-penetrating-peptides
#6
Ly Pärnaste, Piret Arukuusk, Kent Langel, Tanel Tenson, Ülo Langel
Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28620219/molecular-dynamics-exploration-of-poration-and-leaking-caused-by-kalata-b1-in-hiv-infected-cell-membrane-compared-to-host-and-hiv-membranes
#7
Wanapinun Nawae, Supa Hannongbua, Marasri Ruengjitchatchawalya
The membrane disruption activities of kalata B1 (kB1) were investigated using molecular dynamics simulations with membrane models. The models were constructed to mimic the lipid microdomain formation in membranes of HIV particle, HIV-infected cell, and host cell. The differences in the lipid ratios of these membranes caused the formation of liquid ordered (lo) domains of different sizes, which affected the binding and activity of kB1. Stronger kB1 disruptive activity was observed for the membrane with small sized lo domain...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617063/matrix-metalloproteases-responsive-nanomaterials-for-tumor-targeting-diagnosis-and-treatment
#8
Jingyuan Xiong, Huile Gao
Tumor poses tremendous challenges to mankind. In various tumors, matrix metalloproteases (MMPs) are ubiquitously over expressed and participate throughout the process of tumor development. MMPs are commonly used as internal stimuli, and MMPs responsive nanomaterials are classified into three categories according to the drug delivery process: administration and distribution to tumor, intratumoral distribution and cell internalization, and specific drug release. Firstly, MMPs sensitive polyethylene glycol (PEG) de-shielding and activatable cell penetrating peptides were developed to improve the blood circulation time of drug delivery systems, thereby, enhancing tumor or stroma cells recognition and penetration...
June 15, 2017: Journal of Microencapsulation
https://www.readbyqxmd.com/read/28614654/creation-of-a-synthetic-ligand-for-mitochondrial-dna-sequence-recognition-and-promoter-specific-transcription-suppression
#9
Takuya Hidaka, Ganesh N Pandian, Junichi Taniguchi, Tomohiro Nobeyama, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Synthetic ligands capable of recognizing the specific DNA sequences inside human mitochondria and modulating gene transcription is of increasing demand because of the surge in evidence linking mitochondrial genome and diseases. Herein, we created a new type of mitochondria-specific synthetic ligand, termed MITO-PIPs by conjugating a mitochondria-penetrating peptide with pyrrole-imidazole polyamides (PIPs). The designed MITO-PIPs showed specific localization inside mitochondria in HeLa cells and recognized the target DNA in a sequence-specific manner...
June 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28613294/enzymatic-activation-of-cell-penetrating-peptides-in-self-assembled-nanostructures-triggers-fibre-to-micelle-morphological-transition
#10
Yejiao Shi, Yang Hu, Guy Ochbaum, Ran Lin, Ronit Bitton, Honggang Cui, Helena S Azevedo
We report here a proof-of-concept design of a multi-domain cell-penetrating peptide amphiphile (CPPA) which can self-assemble into fibrous nanostructures and transform into spherical micelles upon enzymatic degradation by matrix metalloproteinase-2 (MMP-2) up-regulated in the tumour environment. Concomitant with this morphological transition, the cell-penetrating peptide (CPP), which was previously buried inside the CPPA fibers, could be presented on the surface of the CPPA micelles, enhancing their cell-penetrating ability...
June 14, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28611060/motifs-in-oleosin-target-the-cytosolic-side-of-endoplasmic-reticulum-and-budding-lipid-droplet
#11
Chien Yu Huang, Anthony H C Huang
Plant cytosolic lipid droplets (LDs) are covered with a layer of phospholipids and oleosin and were extensively studied before those in mammals and yeast. Oleosin has short amphipathic N- and C-terminal peptides flanking a conserved 72-residue hydrophobic hairpin, which penetrates and stabilizes the LD. Oleosin is synthesized on endoplasmic reticulum (ER) and extracts ER-budding LDs to cytosol. To delineate the mechanism of oleosin targeting ER-LD, we have expressed modified-oleosin genes in Physcomitrella patens for transient expression and tobacco (Nicotiana tabacum) BY2 cells for stable transformation...
June 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28608690/conformational-plasticity-of-the-cell-penetrating-peptide-sap-as-revealed-by-solid-state-19-f-nmr-and-circular-dichroism-spectroscopies
#12
Sergii Afonin, Vladimir Kubyshkin, Pavel K Mykhailiuk, Igor V Komarov, Anne S Ulrich
The cell-penetrating peptide SAP, which was designed as an amphipathic poly-L-proline helix II (PPII), was suggested to self-assemble into regular fibrils that are relevant for its internalization. Herein we have analyzed the structure of SAP in the membrane-bound state by solid-state (19)F-NMR, which revealed other structural states, in addition to the expected surface-aligned PPII. (2S)-2-Amino-2-[3-(trifluoromethyl)bicyclo[1.1.1]pent-1-yl]ethanoic acid and two rigid isomers of trifluoromethyl-4,5-methanoprolines (CF3-MePro) were used as labels for (19)F-NMR analysis...
June 13, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28603971/enhanced-and-prolonged-cell-penetrating-abilities-of-arginine-rich-peptides-by-introducing-cyclic-%C3%AE-%C3%AE-disubstituted-%C3%AE-amino-acids-with-stapling
#13
Makoto Oba, Masayuki Kunitake, Takuma Kato, Atsushi Ueda, Masakazu Tanaka
Cell-penetrating peptides are receiving increasing attention as drug delivery tools, and the search for peptides with high cell-penetrating ability and negligible cytotoxicity has become a critical research topic. Herein, cyclic α,α-disubstituted α-amino acids were introduced into arginine-rich peptides and an additional staple was provided in the side chain. The peptides designed in the present study showed more enhanced and prolonged cell-penetrating abilities than an arginine nonapeptide due to high resistance to protease and conformationally stable helical structures...
June 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28603674/design-of-new-acid-activated-cell-penetrating-peptides-for-tumor-drug-delivery
#14
Jia Yao, Yinyun Ma, Wei Zhang, Li Li, Yun Zhang, Li Zhang, Hui Liu, Jingman Ni, Rui Wang
TH(AGYLLGHINLHHLAHL(Aib)HHIL-NH2), a histidine-rich, cell-penetrating peptide with acid-activated pH response, designed and synthesized by our group, can effectively target tumor tissues with an acidic extracellular environment. Since the protonating effect of histidine plays a critical role in the acid-activated, cell-penetrating ability of TH, we designed a series of new histidine substituents by introducing electron donating groups (Ethyl, Isopropyl, Butyl) to the C-2 position of histidine. This resulted in an enhanced pH-response and improved the application of TH in tumor-targeted delivery systems...
2017: PeerJ
https://www.readbyqxmd.com/read/28603028/targeting-of-p32-in-peritoneal-carcinomatosis-with-intraperitoneal-lintt1-peptide-guided-pro-apoptotic-nanoparticles
#15
Hedi Hunt, Lorena Simón-Gracia, Allan Tobi, Venkata Ramana Kotamraju, Shweta Sharma, Mait Nigul, Kazuki N Sugahara, Erkki Ruoslahti, Tambet Teesalu
Gastrointestinal and gynecological malignancies disseminate in the peritoneal cavity - a condition known as peritoneal carcinomatosis (PC). Intraperitoneal (IP) administration can be used to improve therapeutic index of anticancer drugs used for PC treatment. Activity of IP anticancer drugs can be further potentiated by encapsulation in nanocarriers and/or affinity targeting with tumor-specific affinity ligands, such as tumor homing peptides. Here we evaluated a novel tumor penetrating peptide, linTT1 (AKRGARSTA), as a PC targeting ligand for nanoparticles...
June 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28602843/combination-of-cell-penetrating-peptides-and-heterologous-dna-prime-protein-boost-strategy-enhances-immune-responses-against-hiv-1-nef-antigen-in-balb-c-mouse-model
#16
Somayeh Kadkhodayan, Behnaz Sadat Jafarzade, Seyed Mehdi Sadat, Fateme Motevalli, Elnaz Agi, Azam Bolhassani
To develop a strong HIV specific T-cell response, the HIV-1 Tat and Nef regulatory proteins have been known as attractive antigenic candidates in vaccine design. A peptide transduction domain of Tat (48-60 aa) could act to deliver other therapeutic molecules into different cells. In this line, several cell-penetrating peptides (CPPs) have been designed to transfer DNA, siRNA, polypeptides and proteins into cells through non-covalent approach such as CADY and PEP families. Some studies showed that the endogenous adjuvants including heat shock protein Gp96 could stimulate antigen-specific T cell immune responses...
June 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28602833/a-novel-il-1ra-pep-fusion-protein-with-enhanced-brain-penetration-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibition-of-oxidative-stress-and-neuroinflammation
#17
Dong-Dong Zhang, Min-Ji Zou, Ya-Tao Zhang, Wen-Liang Fu, Tao Xu, Jia-Xi Wang, Wen-Rong Xia, Zhi-Guang Huang, Xiang-Dong Gan, Xiao-Ming Zhu, Dong-Gang Xu
Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP)...
June 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28599181/adsorption-of-cell-penetrating-peptide-tat2-and-polycation-luviquat-fc-370-to-triticale-microspore-exine
#18
Jordan T Pepper, Priti Maheshwari, François Eudes
Microspores are the pre-gametophyte stage of pollen, and have proven to be a successful tissue culture material for the production of doubled haploid plants. Microspore culture has also been used as a platform for the production of transgenic plants. The use of cell-penetrating peptides (CPPs) as transfection agents in microspores has been previously demonstrated, but at low efficiencies. Here, the pH dependent adsorption of the cationic CPP Tat2 to the sporopollenin surface of the microspore (the exine) has been explored using electrophoretic light scattering (ELS)...
June 3, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28597524/loosening-of-lipid-packing-promotes-oligoarginine-entry-into-cells
#19
Tomo Murayama, Toshihiro Masuda, Sergii Afonin, Kenichi Kawano, Tomoka Takatani-Nakase, Hiroki Ida, Yasufumi Takahashi, Takeshi Fukuma, Anne S Ulrich, Shiroh Futaki
Despite extensive use of arginine-rich cell-penetrating peptides (CPPs)-including octaarginine (R8)-as intracellular delivery vectors, mechanisms for their internalization are still under debate. Lipid packing in live cell membranes was characterized using a polarity-sensitive dye (di-4-ANEPPDHQ), and evaluated in terms of generalized polarization. Treatment with membrane curvature-inducing peptides led to significant loosening of the lipid packing, resulting in an enhanced R8 penetration. Pyrenebutyrate (PyB) is known to facilitate R8 membrane translocation by working as a hydrophobic counteranion...
June 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28586730/a-multifunctional-organosilica-cross-linker-for-the-bio-conjugation-of-gold-nanorods
#20
Sarah Lai, Sonia Centi, Claudia Borri, Fulvio Ratto, Lucia Cavigli, Filippo Micheletti, Bjӧrn Kemper, Steffi Ketelhut, Tatiana Kozyreva, Leonardo Gonnelli, Francesca Rossi, Stefano Colagrande, Roberto Pini
We report on the use of organosilica shells to couple gold nanorods to functional peptides and modulate their physiochemical and biological profiles. In particular, we focus on the case of cell penetrating peptides, which are used to load tumor-tropic macrophages and implement an innovative drug delivery system for photothermal and photoacoustic applications. The presence of organosilica exerts subtle effects on multiple parameters of the particles, including their size, shape, electrokinetic potential, photostability, kinetics of endocytic uptake and cytotoxicity, which are investigated by the interplay of colorimetric methods and digital holographic microscopy...
May 31, 2017: Colloids and Surfaces. B, Biointerfaces
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