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Tat peptide

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https://www.readbyqxmd.com/read/28334537/multivalency-effect-of-tat-peptide-functionalized-nanoparticle-in-cellular-endocytosis-and-subcellular-trafficking
#1
Nikhil R Jana, Chumki Dalal
Although trans-activating transcription (TAT)-peptide functionalized nanoparticle/polymer/liposome is widely used for cellular transfection applications, the multivalency (number of attached peptide per particle) effect on cell uptake mechanism and subcellular targeting performance is largely unexplored. Here we show that multivalency of nanoparticle controls the cellular interaction, cellular entry/exit mechanism and subcellular targeting performance. We have synthesized TAT peptide functionalized quantum dot (QD) of 30-35 nm hydrodynamic diameter with varied multivalency from 10 to 75 (e...
March 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28323576/tat-rasgap317-326-enhances-radiosensitivity-of-human-carcinoma-cell-lines-in-vitro-and-in-vivo-through-promotion-of-delayed-mitotic-cell-death
#2
Pelagia Tsoutsou, Alessandro Annibaldi, David Viertl, Jonathan Ollivier, Franz Buchegger, Marie-Catherine Vozenin, Jean Bourhis, Christian Widmann, Oscar Matzinger
The synthetic peptide TAT-RasGAP317-326 has been shown to potentiate the efficacy of anti-cancer drugs. In this study, we explored the action of TAT-RasGAP317-326 when combined with radiation by investigating its radiosensitizing activity in vitro and in vivo. To investigate the modulation of intrinsic radiosensitivity induced by TAT-RasGAP317-326, clonogenic assays were performed using four human cancer cell lines, HCT116 p53(+/+) (ATCC: CCL-247), HCT116 p53(-/-), PANC-1 (ATCC: CRL-1469) and HeLa (ATCC: CCL-2), as well as one nontumor cell line, HaCaT (CLS: 300493)...
March 21, 2017: Radiation Research
https://www.readbyqxmd.com/read/28322550/multiplex-substrate-profiling-by-mass-spectrometry-for-kinases-reveals-quantitative-substrate-motifs
#3
Nicole Olson Meyer, Anthony J O'Donoghue, Ursula Schulze-Gahmen, Matthew Ravalin, Steven M Moss, Michael B Winter, Giselle M Knudsen, Charles S Craik
The more than 500 protein kinases comprising the human kinome catalyze hundreds of thousands of phosphorylation events to regulate a diversity of cellular functions; however, the extended substrate specificity is still unknown for many of these kinases. We report here a method for quantitatively describing kinase substrate specificity using an unbiased peptide library-based approach with direct measurement of phosphorylation by tandem LC-MS/MS peptide sequencing (Multiplex Substrate Profiling by Mass Spectrometry, MSP-MS)...
March 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28314993/comparative-analysis-of-internalisation-haemolytic-cytotoxic-and-antibacterial-effect-of-membrane-active-cationic-peptides-aspects-of-experimental-setup
#4
Kata Horváti, Bernadett Bacsa, Tamás Mlinkó, Nóra Szabó, Ferenc Hudecz, Ferenc Zsila, Szilvia Bősze
Cationic peptides proved fundamental importance as pharmaceutical agents and/or drug carrier moieties functioning in cellular processes. The comparison of the in vitro activity of these peptides is an experimental challenge and a combination of different methods, such as cytotoxicity, internalisation rate, haemolytic and antibacterial effect, is necessary. At the same time, several issues need to be addressed as the assay conditions have a great influence on the measured biological effects and the experimental setup needs to be optimised...
March 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28286529/a-synthetic-strategy-for-conjugation-of-paromomycin-to-cell-penetrating-tat-48-60-for-delivery-and-visualization-into-leishmania-parasites
#5
Sira Defaus, Maria Gallo, María A Abengózar, Luis Rivas, David Andreu
A successful approach to deliver paromomycin, a poorly absorbed aminoglycoside antibiotic, to parasite cells is reported, based on selective protection of amino and hydroxyl groups followed by conjugation to a fluorolabeled, PEG-functionalized cell-penetrating Tat(48-60) peptide. The resulting construct is efficiently internalized into Leishmania cells, evidencing the fitness of cell-penetrating peptides as vectors for efficiently transporting low-bioavailability drugs into cells.
2017: International Journal of Peptides
https://www.readbyqxmd.com/read/28285195/engineering-intravaginal-vaccines-to-overcome-mucosal-and-epithelial-barriers
#6
Zhonghua Ji, Zhaolu Xie, Zhirong Zhang, Tao Gong, Xun Sun
The mucosal surface of the vagina is a primary human immunodeficiency virus (HIV) entry portal, making it an attractive site for HIV vaccination. However, HIV vaccines based on recombinant adenovirus (rAd) do not efficiently cross the mucus layers or underlying epithelium of the vagina. Here we designed nanocomplexes of rAd particles coated with (1) the polyethylene glycol derivative APS to provide a hydrophilic surface that would prevent entrapment in the hydrophobic mucus, and (2) the cell-penetrating peptide TAT to improve transduction efficiency...
March 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28282092/nir-emitting-and-photo-thermal-active-nanogold-as-mitochondria-specific-probes
#7
Sabyasachi Chakrabortty, Miguel Sison, Yuzhou Wu, Anita Ladenburger, Goutam Pramanik, Johannes Biskupek, Jerome Extermann, Ute Kaiser, Theo Lasser, Tanja Weil
We report a bioinspired multifunctional albumin derived polypeptide coating comprising grafted poly(ethylene oxide) chains, multiple copies of the HIV TAT derived peptide enabling cellular uptake as well as mitochondria targeting triphenyl-phosphonium (TPP) groups. Exploring these polypeptide copolymers for passivating gold nanoparticles (Au NPs) yielded (i) NIR-emitting markers in confocal microscopy and (ii) photo-thermal active probes in optical coherence microscopy. We demonstrate the great potential of such multifunctional protein-derived biopolymer coatings for efficiently directing Au NP into cells and to subcellular targets to ultimately probe important cellular processes such as mitochondria dynamics and vitality inside living cells...
March 10, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28279738/modifying-plasmid-loaded-hsa-nanoparticles-with-cell-penetrating-peptides-cellular-uptake-and-enhanced-gene-delivery
#8
J Mesken, A Iltzsche, D Mulac, K Langer
Gene therapy bears great potential for the cure of a multitude of human diseases. Research efforts focussed on the use of viral delivery vectors in the past decades, neglecting non-viral gene therapies of physical or chemical origin due to low transfection efficiency. However, side effects such as activation of oncogenes and inflammatory reactions upon immune cell activation are major obstacles impeding the clinical applicability of viral gene therapy vectors. The aim of this study was the development of a non-viral gene delivery system based on plasmid-loaded human serum albumin nanoparticles, which are biocompatible, biodegradable, and non-toxic in relevant concentrations...
March 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28263836/optical-barcoding-of-plga-for-multispectral-analysis-of-nanoparticle-fate-in-vivo
#9
David X Medina, Kyle T Householder, Ricki Ceton, Tina Kovalik, John M Heffernan, Rohini V Shankar, Robert P Bowser, Robert J Wechsler-Reya, Rachael W Sirianni
Understanding of the mechanisms by which systemically administered nanoparticles achieve delivery across biological barriers remains incomplete, due in part to the challenge of tracking nanoparticle fate in the body. Here, we develop a new approach for "barcoding" nanoparticles (NPs) composed of poly(lactic-co-glycolic acid) (PLGA) with bright, spectrally defined quantum dots (QDs) to enable direct, fluorescent detection of NP fate with subcellular resolution. We show that QD labeling does not affect major biophysical properties of NPs or their interaction with cells and tissues...
March 2, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28262014/high-efficiency-secretion-of-%C3%AE-mannanase-in-bacillus-subtilis-through-protein-synthesis-and-secretion-optimization
#10
Yafeng Song, Gang Fu, Huina Dong, Jianjun Li, Yuguang Du, Dawei Zhang
The manno endo-1, 4-mannosidase (β-mannanase, EC. 3.2.1.78) catalyzes the random hydrolysis of internal (1→4)-β-mannosidic linkages in the mannan polymers. A codon optimized β-mannanase gene from Bacillus licheniformis DSM13 was expressed in Bacillus subtilis. When four Sec-dependent and two Tat-dependent signal peptide sequences cloned from B. subtilis were placed upstream of the target gene, the highest activity of β-mannanase was observed using SPlipA as a signal peptide. Then, a 1.25-fold activity of β-mannanase was obtained when another copy of groESL operon was inserted into the genome of host strain...
March 6, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28260884/topical-ocular-delivery-to-laser-induced-choroidal-neovascularization-by-dual-internalizing-rgd-and-tat-peptide-modified-nanoparticles
#11
Yongchao Chu, Ning Chen, Huajun Yu, Hongjie Mu, Bin He, Hongchen Hua, Aiping Wang, Kaoxiang Sun
A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. (1)H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)- poly(lactic-co-glycolic acid)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28258543/reducing-mitochondrial-bound-hexokinase-ii-mediates-transition-from-non-injurious-into-injurious-ischemia-reperfusion-of-the-intact-heart
#12
Rianne Nederlof, Ebru Gürel-Gurevin, Otto Eerbeek, Chaoqin Xie, G Sjoerd Deijs, Moritz Konkel, Jun Hu, Nina C Weber, Cees A Schumacher, Antonius Baartscheer, Egbert G Mik, Markus W Hollmann, Fadi G Akar, Coert J Zuurbier
Ischemia/reperfusion (I/R) of the heart becomes injurious when duration of the ischemic insult exceeds a certain threshold (approximately ≥20 min). Mitochondrial bound hexokinase II (mtHKII) protects against I/R injury, with the amount of mtHKII correlating with injury. Here, we examine whether mtHKII can induce the transition from non-injurious to injurious I/R, by detaching HKII from mitochondria during a non-injurious I/R interval. Additionally, we examine possible underlying mechanisms (increased reactive oxygen species (ROS), increased oxygen consumption (MVO2) and decreased cardiac energetics) associated with this transition...
March 3, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28229590/impacts-of-cross-linkers-on-biological-effects-of-mesoporous-silica-nanoparticles
#13
Yi-Ping Chen, Si-Han Wu, I-Chih Chen, Chien-Tsu Chen
Chemically synthesized cross-linkers play decisive roles in variable cargos attached to nanoparticles (NPs). Previous studies reported that surface properties, such as the size, charge, and surface chemistry, are particularly important determinants influencing the biological fate and actions of NPs and cells. Recent studies also focused on the relationship of serum proteins with the surface properties of NPs (also called the protein corona), which is recognized as a key factor in determining the cytotoxicity and biodistribution...
March 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28223511/a-signal-sequence-suppressor-mutant-that-stabilizes-an-assembled-state-of-the-twin-arginine-translocase
#14
Qi Huang, Felicity Alcock, Holger Kneuper, Justin C Deme, Sarah E Rollauer, Susan M Lea, Ben C Berks, Tracy Palmer
The twin-arginine protein translocation (Tat) system mediates transport of folded proteins across the cytoplasmic membrane of bacteria and the thylakoid membrane of chloroplasts. The Tat system of Escherichia coli is made up of TatA, TatB, and TatC components. TatBC comprise the substrate receptor complex, and active Tat translocases are formed by the substrate-induced association of TatA oligomers with this receptor. Proteins are targeted to TatBC by signal peptides containing an essential pair of arginine residues...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28218748/hiv-tat-protein-and-amyloid-%C3%AE-peptide-form-multifibrillar-structures-that-cause-neurotoxicity
#15
Alina Hategan, Mario A Bianchet, Joseph Steiner, Elena Karnaukhova, Eliezer Masliah, Adam Fields, Myoung-Hwa Lee, Alex M Dickens, Norman Haughey, Emilios K Dimitriadis, Avindra Nath
Deposition of amyloid-β plaques is increased in the brains of HIV-infected individuals, and the HIV transactivator of transcription (Tat) protein affects amyloidogenesis through several indirect mechanisms. Here, we investigated direct interactions between Tat and amyloid-β peptide. Our in vitro studies showed that in the presence of Tat, uniform amyloid fibrils become double twisted fibrils and further form populations of thick unstructured filaments and aggregates. Specifically, Tat binding to the exterior surfaces of the Aβ fibrils increases β-sheet formation and lateral aggregation into thick multifibrillar structures, thus producing fibers with increased rigidity and mechanical resistance...
February 20, 2017: Nature Structural & Molecular Biology
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
#16
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/28193523/faah-inhibition-produces-antidepressant-like-efforts-of-mice-to-acute-stress-via-synaptic-long-term-depression
#17
Ying Wang, Xia Zhang
Recent studies have shown that inhibition of fatty acid amide hydrolase (FAAH), the major degradative enzyme of the endocannabinoid N-arachidonoylethanolamine (AEA), produced antidepressant behavioral responses, but its underlying mechanism is not clear. Here we find that a systemic administration of the FAAH inhibitor PF3845 or an intra-CA1 application of AEA elicits an in vivo long-term depression (LTD) at excitatory glutamatergic CA3-CA1 synapses of the hippocampus. The PF3845- and/or AEA-elicited LTD are abolished by the LTD-blocking peptide Tat-GluR2...
May 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28193017/single-particle-tracking-of-peptides-modified-nanocargo-on-lipid-membrane-revealing-bulk-mediated-diffusion
#18
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/28190655/development-of-helix-stabilized-cell-penetrating-peptides-containing-cationic-%C3%AE-%C3%AE-disubstituted-amino-acids-as-helical-promoters
#19
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/28187919/dopamine-d3-and-acetylcholine-nicotinic-receptor-heteromerization-in-midbrain-dopamine-neurons-relevance-for-neuroplasticity
#20
Leonardo Bontempi, Paola Savoia, Federica Bono, Chiara Fiorentini, Cristina Missale
Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer(2) (BRET(2)) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET(2) showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR...
February 7, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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