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Tat peptide

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https://www.readbyqxmd.com/read/28530637/cell-penetrating-peptides-selectively-targeting-smad3-inhibit-profibrotic-tgf-%C3%AE-signaling
#1
Jeong-Han Kang, Mi-Yeon Jung, Xueqian Yin, Mahefatiana Andrianifahanana, Danielle M Hernandez, Edward B Leof
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28515319/the-h-region-of-twin-arginine-signal-peptides-supports-productive-binding-of-bacterial-tat-precursor-proteins-to-the-tatbc-receptor-complex
#2
Agnes Ulfig, Julia Fröbel, Frank Lausberg, Anne-Sophie Blümmel, Anna Katharina Heide, Matthias Müller, Roland Freudl
The twin arginine translocation (Tat) pathway transports folded proteins across bacterial membranes. Tat precursor proteins possess a conserved twin-arginine (RR) motif in their signal peptides that is involved in their binding to the Tat translocase, but some facets of this interaction remain unclear. Here, we investigated the role of the hydrophobic (h-) region of the Escherichia coli TMAO reductase (TorA) signal peptide in TatBC receptor binding in vivo and in vitro. We show that besides the RR motif, a minimal functional h-region in the signal peptide is required for Tat-dependent export in E...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28490747/structural-basis-for-importin-%C3%AE-binding-of-the-human-immunodeficiency-virus-tat
#3
K M Smith, Z Himiari, S Tsimbalyuk, J K Forwood
HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning (48)GRKKRR, and a cell penetrating peptide (CPP) signal spanning (48)GRKKRRQRRRAPQN...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483976/targeting-a-potassium-channel-syntaxin-interaction-ameliorates-cell-death-in-ischemic-stroke
#4
Chung-Yang Yeh, Ashlyn M Bulas, Aubin Moutal, Jami L Saloman, Karen A Hartnett, Charles T Anderson, Thanos Tzounopoulos, Dandan Sun, Rajesh Khanna, Elias Aizenman
The voltage-gated K(+) channel Kv2.1 has been intimately linked with neuronal apoptosis. After ischemic, oxidative, or inflammatory insults, Kv2.1 mediates a pronounced, delayed enhancement of K(+) efflux, generating an optimal intracellular environment for caspase and nuclease activity, key components of programmed cell death. This apoptosis-enabling mechanism is initiated via Zn(2+)-dependent dual phosphorylation of Kv2.1, increasing the interaction between the channel's intracellular C-terminus domain and the SNARE protein syntaxin 1A...
May 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28482272/screening-of-commercial-cyclic-peptide-conjugated-to-hiv-1-tat-peptide-as-inhibitor-of-n-terminal-heptad-repeat-glycoprotein-2-ectodomain-ebola-virus-through-in-silico-analysis
#5
Usman Sumo Friend Tambunan, Ahmad Husein Alkaff, Mochammad Arfin Fardiansyah Nasution, Arli Aditya Parikesit, Djati Kerami
Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism...
April 21, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28468542/cell-penetrating-peptide-conjugates-to-enhance-the-antitumor-effect-of-paclitaxel-on-drug-resistant-lung-cancer
#6
Ziqing Duan, Cuitian Chen, Jing Qin, Qi Liu, Qi Wang, Xinchun Xu, Jianxin Wang
To conquer the drug resistance of tumors and the poor solubility of paclitaxel (PTX), two PTX-cell-penetrating peptide conjugates (PTX-CPPs), PTX-TAT and PTX-LMWP, were synthesized and evaluated for the first time. Compared with free PTX, PTX-CPPs displayed significantly enhanced cellular uptake, elevated cell toxicity, increased cell apoptosis, and decreased mitochondrial membrane potential (Δψm) in both A549 and A549T cells. PTX-LMWP exhibited a stronger inhibitory effect than PTX-TAT in A549T cells. Analysis of cell-cycle distribution showed that PTX-LMWP influenced mitosis in drug-resistant A549T tumor cells via a different mechanism than PTX...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28462721/the-expression-and-purification-of-the-delta-sleep-inducing-peptide-fused-with-protein-transduction-domain-and-human-serum-albumin-in-pichia-pastoris
#7
Xin-Guo Zhang, Wen-Na Wang, Chun-Sheng Zhang, Kun Li, Guo-Di Ma, Jian-Yong Li
Delta sleep-inducing peptide (DSIP) is a nonapeptide that could promote sleep through the induction of slow wave sleep. To further study the pharmacological effect of DSIP on insomnia, we designed a fusion protein containing N-terminal TAT-based transduction domain followed by human serum albumin and DSIP and designated this protein as PHD fusion protein. We expressed PHD fusion protein in Pichia pastoris, purified it to near homogeneity by three-step chromatography and performed bioactivity assay. The pharmacological activity of PHD fusion protein was studied using classic pentobarbital-induced sleep test in healthy mice...
April 25, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28460227/transcription-activator-hyaluronic-acid-and-tocopheryl-succinate-multi-functionalized-novel-lipid-carriers-encapsulating-etoposide-for-lymphoma-therapy
#8
Hongyun Wang, Guodong Sun, Zhigang Zhang, Yang Ou
Delivery of chemotherapeutic drugs using nanocarriers is emerging as a promising approach for the treatment of cancer. The aim of this research was to develop a dual targeted d-α-tocopheryl succinate (TOS) functionalized nanostructured lipid carriers (NLCs), using etoposide (ETP) as a model drug to prove their in vitro and in vivo anti-tumor effects. Novel ETP loaded NLCs were constructed (ETP-NLCs). Hyaluronic acid (HA) and cell-penetrating peptide transcription activator (TAT) was applied for the surface decoration of ETP NLCs (HATOS/TATTOS-ETP-NLCs)...
April 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28450931/cell-penetrating-peptide-of-sodium-iodide-symporter-effect-on-the-i-131-radiotherapy-on-thyroid-cancer
#9
Yi-Xiang Fan, Zhi-Xin Liang, Qing-Zhu Liu, Han Xiao, Ke-Bin Li, Ji-Zhen Wu
The aim of the present study was to clarify whether the cell penetrating peptide of sodium-iodide symporter (NIS) has an effect on the I-131 radiotherapy of thyroid cancer. Firstly, we combined the HIV-1 TAT peptide (a cell penetrating peptide, dTAT) and established a nanoparticle vector (dTAT NP) to study the delivery efficiency of this cell-penetrating strategy for tumor-targeted gene delivery. dTAT NP was transfected into cultured TPC-1 cells as a model to study the effects of I-131 radiotherapy on thyroid cancer...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28450191/targeting-neuronal-nitric-oxide-synthase-by-a-cell-penetrating-peptide-tat-lk15-sirna-bioconjugate
#10
Jie Peng, Yun Rao, Xue Yang, Ji Jia, Youping Wu, Jianhua Lu, Yuanxiang Tao, Weifeng Tu
We developed a cell penetrating peptide (CPP) Tat-LK15, as a siRNA carrier to target nNOS. The feasibility, stability, efficiency and selectivity of this peptide-siRNA complex were evaluated in rat neuronal cells. We also compared the new method with conventional siRNA carrier Lipofectamine™. It was found that the CPP Tat-LK15 effectively and specifically delivered nNOS-siRNA into Rat retinal ganglia (RGC-5) cells and silenced the expression of nNOS. The CPP Tat-LK15 can conjugate with siRNA to form stable complex at a ratio of 2:1 (peptide/siRNA, w/w), which maintained stable in serum for as long as 4h...
April 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28442909/tat-functionalized-liposomes-for-the-treatment-of-meningitis-an-in-vitro-study
#11
Caterina Bartomeu Garcia, Di Shi, Thomas J Webster
Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47-57, which is a peptide derived from the Tat protein of HIV)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28437627/tumor-acidity-activatable-tat-targeted-nanomedicine-for-enlarged-fluorescence-magnetic-resonance-imaging-guided-photodynamic-therapy
#12
Meng Gao, Feng Fan, Dongdong Li, Yue Yu, Kuirong Mao, Tianmeng Sun, Haisheng Qian, Wei Tao, Xianzhu Yang
Nanoparticles simultaneously integrated the photosensitizers and diagnostic agents represent an emerging approach for imaging-guided photodynamic therapy (PDT). However, the diagnostic sensitivity and therapeutic efficacy of nanoparticles as well as the heterogeneity of tumors pose tremendous challenges for clinical imaging-guided PDT treatment. Herein, a polymeric nanoparticle with tumor acidity (pHe)-activatable TAT targeting ligand that encapsulates the photosensitizer chlorin e6 (Ce6) and chelates contrast agent Gd(3+) is successfully developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided precision PDT...
April 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28435837/staphylococcus-aureus-type-i-signal-peptidase-essential-or-not-essential-that-s-the-question
#13
COMMENT
Wouter L Hazenbos, Elizabeth Skippington, Man-Wah Tan
Secretion of proteins into the extracellular environment is crucial for the normal physiology and virulence of pathogenic bacteria. Type I signal peptidase (SPase I) mediates the final step of bacterial secretion, by cleaving proteins at their signal peptide once they are translocated by the Sec or twin-arginine (Tat) translocon. SPase I has long been thought to be essential for viability in multiple bacterial pathogens. Challenging this view, we and others have recently created Staphylococcus aureus bacteria lacking the SPase I SpsB that are viable and able to grow in vitro when over-expressing a native gene cassette encoding for a putative ABC transporter...
March 17, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28430962/ulk1-prevents-cardiac-dysfunction-in-obesity-through-autophagy-meditated-regulation-of-lipid-metabolism
#14
Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28421460/flow-arrest-intra-arterial-delivery-of-small-tat-decorated-and-neutral-micelles-to-gliomas
#15
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/28385674/human-derived-fusogenic-peptides-for-the-intracellular-delivery-of-proteins
#16
Kei Sudo, Keisuke Niikura, Kouta Iwaki, Shunshi Kohyama, Kei Fujiwara, Nobuhide Doi
The cytosolic delivery of therapeutic proteins (e.g., antibodies or enzymes) by cell-penetrating peptides (CPPs), such as a human immunodeficiency virus-derived TAT peptide, is facilitated by fusogenic peptides (FPs). For instance, we recently demonstrated that an FP, B18, which is derived from a sea urchin gamete fusion protein, promotes endosomal escape of an enhanced green fluorescent protein (eGFP)-TAT fusion protein directly conjugated to it. However, the potential clinical use of FPs raises concerns because all conventional FPs are non-human-derived...
April 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28375632/tumor-acidity-nir-controlled-interaction-of-transformable-nanoparticle-with-biological-systems-for-cancer-therapy
#17
Dongdong Li, Yinchu Ma, Jinzhi Du, Wei Tao, Xiaojiao Du, Xianzhu Yang, Jun Wang
Precisely controlling the interaction of nanoparticles with biological systems (nanobio interactions) from the injection site to biological targets shows great potential for biomedical applications. Inspired by the ability of nanoparticles to alter their physicochemical properties according to different stimuli, we explored the tumor acidity and near-infrared (NIR) light activated transformable nanoparticle (DA)TAT-NPIR&DOX. This nanoparticle consists of a tumor acidity-activated TAT [the TAT lysine residues' amines was modified with 2,3-dimethylmaleic anhydride (DA)], a flexible chain polyphosphoester core coencapsulated a NIR dye IR-780, and DOX (doxorubicin)...
April 11, 2017: Nano Letters
https://www.readbyqxmd.com/read/28372987/disrupting-sensitization-of-trpv4
#18
Konrad Mack, Michael J M Fischer
TRPV4 ion channels have a broad expression profile and were shown to contribute to enhanced pain sensation in inflammation. Directly blocking TRPV4 might run the risk of interfering with normal physiology, and has prompted to explore the interaction with the scaffolding protein AKAP79, an approach successfully used for TRPV1 channels. HEK293t cells express AKAP79, additional transfection did not sensitize human TRPV4. Application of trypsin facilitated responses to TRPV4 agonist GSK1016790A. Using a specific protease-activated receptor 2 agonist, involvement of an A-kinase anchoring protein in TRPV4 activation was demonstrated by inhibition with AKAP inhibitor peptide Ht31...
June 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28369936/the-role-played-by-oxidative-stress-in-evoking-the-exercise-pressor-reflex-in-health-and-simulated-peripheral-artery-disease
#19
Jonathan E Harms, J Matthew Kuczmarski, Joyce Kim, Gail D Thomas, Marc P Kaufman
Contraction of muscle evokes the exercise pressor reflex (EPR), which is expressed partly by increases in heart rate and arterial pressure. Patients with peripheral artery disease (PAD) show an exaggerated EPR, sometimes report pain when walking and are at risk for cardiac arrthymias. Previous research suggested that reactive oxygen species (ROS) mediate the exaggerated EPR associated with PAD. To examine the effects of ROS on the EPR, we infused a superoxide scavenger, tiron, into the superficial epigastric artery of decerebrated rats...
March 28, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28368124/development-of-surface-variable-polymeric-nanoparticles-for-drug-delivery-to-tumors
#20
Ning Han, Liang Pang, Jun Xu, Hyesun Hyun, Jinho Park, Yoon Yeo
To develop nanoparticle drug carriers that interact with cells specifically in the mildly acidic tumor microenvironment, we produced polymeric nanoparticles modified with amidated TAT peptide via a simple surface modification method. Two types of core poly(lactic-co-glycolic acid) nanoparticles (NL and NP) were prepared with a phospholipid shell as an optional feature and covered with polydopamine that enabled the conjugation of TAT peptide on the surface. Subsequent treatment with acid anhydrides such as cis-aconitic anhydride (CA) and succinic anhydride (SA) converted amines of lysine residues in TAT peptide to β-carboxylic amides, introducing carboxylic groups that undergo pH-dependent protonation and deprotonation...
April 11, 2017: Molecular Pharmaceutics
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