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Tat peptide

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https://www.readbyqxmd.com/read/28096156/bacterial-derived-cell-penetrating-peptides-deliver-gentamicin-to-kill-intracellular-pathogens
#1
Marta Gomarasca, Thaynan F C Martins, Lilo Greune, Philip R Hardwidge, M Alexander Schmidt, Christian Rüter
Commonly used antimicrobials show poor cellular uptake and often have limited access to intracellular targets, resulting in low antimicrobial activity against intracellular pathogens. An efficient delivery system to transport these drugs to the intracellular site of action is needed. Cell-penetrating peptides (CPPs) mediate the internalization of biologically active molecules into the cytoplasm. Here we characterized two CPPs, α1H and α2H, derived from the Y. enterocolitica YopM effector protein. These CPPs, as well as Tat(Trans-activator of transcription) from HIV-1 virus, were used to deliver the antibiotic gentamicin to target intracellular bacteria...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28093948/design-and-evaluation-of-a-stearylated-multicomponent-peptide-sirna-nanocomplex-for-efficient-cellular-sirna-delivery
#2
Yu Wan, Peter M Moyle, Pei Z Gn, Istvan Toth
AIM: To develop a new synthetic peptide-based nanoparticulate siRNA delivery system. MATERIALS & METHODS: DEN-K(GALA)-TAT-K(STR) was generated by incorporating stearic acid into a multicomponent peptide (DEN-K(GALA)-TAT), containing a cationic poly-L-lysine dendron, an endosome-disrupting peptide GALA and a cell-penetrating peptide TAT(48-60). Its physicochemical characteristics, size, toxicity, cellular uptake and gene knockdown activity of the peptide/siRNA complexes were studied...
January 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28092646/ex-vivo-nonviral-gene-delivery-of-%C3%AE-opioid-receptor-to-attenuate-cancer-induced-pain
#3
Seiichi Yamano, Chi T Viet, Dongmin Dang, Jisen Dai, Shigeru Hanatani, Tadahiro Takayama, Hironori Kasai, Kentaro Imamura, Ron Campbell, Yi Ye, John C Dolan, William Myung Kwon, Stefan D Schneider, Brian L Schmidt
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells...
February 2017: Pain
https://www.readbyqxmd.com/read/28069824/arta-dependent-processing-of-a-tat-substrate-containing-a-conserved-tripartite-structure-that-is-not-localized-at-the-c-terminus
#4
Mohd Farid Abdul Halim, Jonathan D Stoltzfus, Stefan Schulze, Micheal Hippler, Mechthild Pohlschroder
: Most prokaryotic secreted proteins are transported to the cell surface using either the general secretion (Sec) or twin arginine translocation (Tat) pathway. A majority of secreted proteins are anchored to the cell surface while the remainder are released into the extracellular environment. The anchored surface proteins play a variety of important roles in cellular processes, ranging from facilitating interactions between cells to maintaining cell stability. The extensively studied S-layer glycoprotein (SLG) of Haloferax volcanii, previously thought to be anchored via C-terminal intercalation into the membrane, was recently shown to be lipidated and to have its C-terminal segment removed in processes dependent upon archaeosortase A (ArtA), a recently discovered enzyme...
January 9, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28065271/signal-peptidase-enzymology-and-substrate-specificity-profiling
#5
R E Dalbey, D Pei, Ö D Ekici
Signal peptidases are membrane proteases that play crucial roles in the protein transport pathway of bacteria. They cleave off the signal peptide from precursor proteins that are membrane inserted by the SecYEG or Tat translocons. Signal peptide cleavage releases the translocated protein from the inner membrane allowing the protein to be exported to the periplasm, outer membrane, or secreted into the medium. Signal peptidases are very important proteins to study. They are unique serine proteases with a Ser-Lys dyad, catalyze cleavage at the membrane surface, and are promising potential antibacterial drug targets...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28051846/selective-intracellular-delivery-of-ganglioside-gm3-binding-peptide-through-caveolae-raft-mediated-endocytosis
#6
Teruhiko Matsubara, Ryohei Otani, Miki Yamashita, Haruka Maeno, Hanae Nodono, Toshinori Sato
Glycosphingolipids are major components of the membrane raft, and several kinds of viruses and bacterial toxins are known to bind to glycosphingolipids in the membrane raft. Since the viral genes and pathogenic proteins that are taken into cells are directly delivered to their target organelles, caveolae/raft-mediated endocytosis represents a promising pathway for specific delivery. In the present study, we demonstrated the ability of an artificial pentadecapeptide, which binds to ganglioside GM3, to deliver protein into cells by caveolae/raft-mediated endocytosis...
January 4, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28045701/unexpected-heat-shock-element-binding-ability-and-tumor-killing-activity-of-the-combinatorial-function-domain-of-apoptin
#7
Liqiu Zhang, Jia Yang, Lu Liu, Wei Tian, Ming Gao, Weiwei Song, Hong Ling, Xingli Dong
Apoptin, derived from the chicken anemia virus, has been found to exert tumor-preferential apoptotic activity. It is a potential anticancer agent with direct clinical applications. However, if this viral protein were to be used as a new drug, it might also induce a strong immune response, causing toxic side effects. In a previous study, our group showed that TAT-apoptin downregulates the stress expression of heat shock protein 70 by competing with heat shock factor protein 1 in binding to the heat shock element (HSE) of the promoter region of heat shock protein 70, thus inducing specific apoptosis in HepG2 cells...
December 29, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28044164/a-peptide-functionalized-nanomotor-as-an-efficient-cell-penetrating-tool
#8
Fei Peng, Yingfeng Tu, Ashish Adhikari, Jordi C J Hintzen, Dennis W P M Löwik, Daniela A Wilson
A nanomotor based strategy for fast cellular entry and cargo delivery is presented. The concept focuses on integrating tat peptide, a basic domain of HIV-1 tat protein, with state of the art nanomotors which possess attractive autonomous properties, facilitating cellular penetration and uptake. The rapid cellular internalization process leads to higher delivery efficiency.
January 3, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28005379/hiv-peptide-mediated-binding-behaviors-of-nanoparticles-on-lipid-membrane
#9
Minh Dinh Phan, Heesuk Kim, Songyi Lee, Chung-Jong Yu, Bongjin Moon, Kwanwoo Shin
Bioinspired design of ligands for nanoparticle coating with remarkable precision in controlling anisotropic connectivity and with universal binding efficiency to the membrane have made a great impact on nanoparticle self-assembly. We utilize HIV-1 derived trans-activator of transcription peptide (TAT), a member of the cell-penetrating peptides, as a soft shell coating on gold nanoparticles (GNPs), and characterize TAT pepide-mediated binding behaviors of GNPs on the lipid membrane. Whereas the peptides enable GNPs to firmly attach to the membrane, the binding structures are driven by two electrostatic forces: the interparticle peptide-repulsion and the peptide-membrane attraction...
December 22, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28002966/development-of-small-molecules-with-a-noncanonical-binding-mode-to-hiv-1-trans-activation-response-tar-rna
#10
Fardokht A Abulwerdi, Matthew D Shortridge, Joanna Sztuba-Solinska, Robert Wilson, Stuart F J Le Grice, Gabriele Varani, John S Schneekloth
Small molecules that bind to RNA potently and specifically are relatively rare. The study of molecules that bind to the HIV-1 transactivation response (TAR) hairpin, a cis-acting HIV genomic element, has long been an important model system for the chemistry of targeting RNA. Here we report the synthesis, biochemical, and structural evaluation of a series of molecules that bind to HIV-1 TAR RNA. A promising analogue, 15, retained the TAR binding affinity of the initial hit and displaced a Tat-derived peptide with an IC50 of 40 μM...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28000363/native-top-down-mass-spectrometry-of-tar-rna-in-complexes-with-a-wild-type-tat-peptide-for-binding-site-mapping
#11
Eva-Maria Schneeberger, Kathrin Breuker
Ribonucleic acids (RNA) frequently associate with proteins in many biological processes to form more or less stable complex structures. The characterization of RNA-protein complex structures and binding interfaces by nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, or strategies based on chemical crosslinking, however, can be quite challenging. Herein, we have explored the use of an alternative method, native top-down mass spectrometry (MS), for probing of complex stoichiometry and protein binding sites at the single-residue level of RNA...
December 21, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27992601/a-novel-functional-domain-of-tab2-involved-in-the-interaction-with-estrogen-receptor-alpha-in-breast-cancer-cells
#12
Stefania Reineri, Silvia Agati, Valentina Miano, Monica Sani, Paola Berchialla, Laura Ricci, Andrea Iannello, Lucia Coscujuela Tarrero, Santina Cutrupi, Michele De Bortoli
Tab2, originally described as a component of the inflammatory pathway, has been implicated in phenomena of gene de-repression in several contexts, due to its ability to interact with the NCoR corepressor. Tab2 interacts also with steroid receptors and dismisses NCoR from antagonist-bound Estrogen and Androgen Receptors on gene regulatory regions, thus modifying their transcriptional activity and leading to pharmacological resistance in breast and prostate cancer cells. We demonstrated previously that either Tab2 knock-down, or a peptide mimicking the Estrogen Receptor alpha domain interacting with Tab2, restore the antiproliferative response to Tamoxifen in Tamoxifen-resistant breast cancer cells...
2016: PloS One
https://www.readbyqxmd.com/read/27987133/tat-pep-enhanced-neurobehavioral-functional-recovery-by-facilitating-axonal-regeneration-and-corticospinal-tract-projection-after-stroke
#13
Bin Deng, Liya Li, Xingchun Gou, Hao Xu, Zhaohua Zhao, Qiang Wang, Lixian Xu
Paired immunoglobulin-like receptor B (PirB) has been identified as a new receptor for myelin-associated inhibitory (MAI) proteins, which may play important role in axonal regeneration and corticospinal tract (CST) projection associated with neurobehavioral function recovery after stroke. Here, we found that the expression of PirB was increased in the cortical penumbra from 1 to 28 days after transient focal cerebral ischemic reperfusion of rats. Then, transactivator of transcription-PirB extracellular peptide (TAT-PEP) was generated that might block the interactions between MAIs and PirB...
December 16, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27941629/the-telomerase-derived-anticancer-peptide-vaccine-gv1001-as-an-extracellular-heat-shock-protein-mediated-cell-penetrating-peptide
#14
REVIEW
Hong Kim, Eun-Hye Seo, Seung-Hyun Lee, Bum-Joon Kim
Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes...
December 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27940360/a-new-fluorescence-based-method-to-monitor-the-ph-in-the-thylakoid-lumen-using-gfp-variants
#15
Hong Yang, Xiaojun Pu, Lu Wang, Li Liu, Steven M Theg
The ΔpH-dependent/Tat pathway is unique for using only proton motive force for driving proteins transport across the thylakoid membrane in chloroplasts among five different pathways. 9-aminoacridine fluorescence quenching is widely used to monitor the ΔpH developed across the thylakoid membrane in the light. However, this method suffers from limited sensitivity to low ΔpH values and to spurious fluorescence signals due to membrane binding. In order to develop a more sensitive method for monitoring the real pH of the thylakoid lumen without these problems we transformed Arabidopsis thaliana with a ratiometric pH sensitive GFP variant (termed pHluorin) targeted to the lumen by the prOE17 transit peptide...
December 8, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27936394/increased-intracellular-ca-2-decreases-cisplatin-resistance-by-regulating-inos-expression-in-human-ovarian-cancer-cells
#16
Yang Yu, Qi Xie, Weimin Liu, Yuting Guo, Na Xu, Lu Xu, Shibing Liu, Songyan Li, Ye Xu, Liankun Sun
Previous studies have reported that intracellular Ca(2+) signals and inducible nitric oxide synthase (iNOS) are involved in cell apoptosis. However, the role of iNOS in cisplatin resistance in ovarian cancer remains unclear. Here, we demonstrate that SKOV3/DDP ovarian cancer cells were more resistant to cisplatin than were SKOV3 ovarian cancer cells. The expression of intracellular Ca(2+) and iNOS was more strongly induced by cisplatin in SKOV3 cells than in SKOV3/DDP cells. TAT-conjugated IP3R-derived peptide (TAT-IDP(S)) increased cisplatin-induced iNOS expression and apoptosis in SKOV3/DDP cells...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27935984/a-biodegradable-polyethylenimine-based-vector-modified-by-trifunctional-peptide-r18-for-enhancing-gene-transfection-efficiency-in-vivo
#17
Jing Hu, Manman Zhu, Kehai Liu, Hua Fan, Wenfang Zhao, Yuan Mao, Yaguang Zhang
Lack of capacity to cross the nucleus membrane seems to be one of the main reasons for the lower transfection efficiency of gene vectors observed in vivo study than in vitro. To solve this problem, a new non-viral gene vector was designed. First, a degradable polyethylenimine (PEI) derivate was synthesized by crosslinking low-molecular-weight (LMW) PEI with N-octyl-N-quaternary chitosan (OTMCS), and then adopting a designed trifunctional peptide (RGDC-TAT-NLS) with good tumor targeting, cell uptake and nucleus transport capabilities to modify OTMCS-PEI...
2016: PloS One
https://www.readbyqxmd.com/read/27933338/progress-in-research-and-application-of-hiv-1-tat-derived-cell-penetrating-peptide
#18
REVIEW
Le Zou, Qilin Peng, Ping Wang, Boting Zhou
Human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) is encoded by HIV-1. It is a peptide rich in basic amino acids and belongs to the protein transduction domain family. It has been found that HIV-1 TAT and its core peptide segment TAT47-57 play an important role in promoting the cellular uptake of coupled bioactive macromolecules, such as peptides, proteins, oligonucleotides, and drug molecules. HIV-1 TAT can also significantly increase the soluble expression of extrinsic proteins...
December 8, 2016: Journal of Membrane Biology
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#19
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek R Clements, Youra Kim, Patrick W K Lee, Shashi A Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929127/lipid-modified-g4-decoy-oligonucleotide-anchored-to-nanoparticles-delivery-and-bioactivity-in-pancreatic-cancer-cells
#20
S Cogoi, U Jakobsen, E B Pedersen, S Vogel, L E Xodo
KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription factor essential for KRAS transcription. It is based on the use of palmitoyl-oleyl-phosphatidylcholine (POPC) liposomes functionalized with lipid-modified G4-decoy oligonucleotides and a lipid-modified cell penetrating TAT peptide...
December 8, 2016: Scientific Reports
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