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Cell penetrating 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/28094952/effect-of-an-enhanced-nose-to-brain-delivery-of-insulin-on-mild-and-progressive-memory-loss-in-the-senescence-accelerated-mouse
#2
Noriyasu Kamei, Misa Tanaka, Hayoung Choi, Nobuyuki Okada, Takamasa Ikeda, Rei Itokazu, Mariko Takeda-Morishita
Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28093948/design-and-evaluation-of-a-stearylated-multicomponent-peptide-sirna-nanocomplex-for-efficient-cellular-sirna-delivery
#3
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/28093876/development-of-poly-lactide-co-glycolide-nanoparticles-functionalized-with-a-mitochondria-penetrating-peptide
#4
Francesca Selmin, Giulia Magri, Chiara G M Gennari, Silvia Marchianò, Nicola Ferri, Sara Pellegrino
The development of mitochondria-targeting cell permeable vectors represents a promising therapeutic approach for several diseases, such as cancer and oxidative pathologies. Nevertheless, access to mitochondria can be difficult. A new hybrid material composed by poly(lactide-co-glycolide) (PLGA) functionalized with a 6-mer mitochondria penetrating peptide (MPP), consisting in alternating arginine and unnatural cyclohexylalanine, was developed. Circular dichroism, FT-IR and DSC studies indicated that the conjugation of the peptide with the polymer led to the obtainment of a more rigid material with respect to both PLGA and MPP as such...
January 17, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28090686/effectively-enhancing-cytotoxic-and-apoptotic-effects-of-alpha-momorcharin-by-integrating-a-heparin-binding-peptide
#5
Meng-Jie Tan, Xue-Wei Cao, Peng-Fei Li, Yi-Zhou Zhai, Yu Zhou, Ye-Jun Liu, Jian Zhao, Fu-Jun Wang
Alpha-momorcharin (α-MMC), a type I ribosome inactivating protein, has attracted a great deal attention because of its antitumor activity. However, the cytotoxicity of α-MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of α-MMC, a heparin-binding domain derived from HB-EGF (named HBP) was used as a cell-penetrating peptide and fused to the C-terminus of α-MMC. This novel α-MMC-HBP fusion protein was expressed and purified with a Ni(2+) -resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of α-MMC...
January 16, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28080251/tetrahedral-dna-nanoparticle-vector-for-intracellular-delivery-of-targeted-peptide-nucleic-acid-antisense-agents-to-restore-antibiotic-sensitivity-in-cefotaxime-resistant-escherichia-coli
#6
John Benedict Readman, George Dickson, Nick G Coldham
The bacterial cell wall presents a barrier to the uptake of unmodified synthetic antisense oligonucleotides, such as peptide nucleic acids, and so is one of the greatest obstacles to the development of their use as therapeutic anti-bacterial agents. Cell-penetrating peptides have been covalently attached to antisense agents, to facilitate penetration of the bacterial cell wall and deliver their cargo into the cytoplasm. Although they are an effective vector for antisense oligonucleotides, they are not specific for bacterial cells and can exhibit growth inhibitory properties at higher doses...
January 12, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28078813/host-defense-peptide-derived-privileged-scaffolds-for-anti-infective-drug-discovery
#7
Ersilia Nigro, Irene Colavita, Daniela Sarnataro, Olga Scudiero, Aurora Daniele, Francesco Salvatore, Antonello Pessi
'Privileged scaffolds' are molecular frameworks which have been successfully exploited for small molecule drug discovery. Peptide privileged scaffolds, featuring a strictly conserved multiple-disulfide framework and high variability in the rest of the sequence, display a broad range of biological effects, including antimicrobial and antiviral activity. Unlike small molecules, however, the cost of manufacturing these peptides is high, and their synthesis challenging. We previously described a simplified privileged scaffold corresponding to the γ-core of human β-defensin-3 (HBD3)...
January 12, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28067008/histidine-rich-designer-peptides-of-the-lah4-family-promote-cell-delivery-of-a-multitude-of-cargo
#8
Gilles Moulay, Christian Leborgne, A James Mason, Christopher Aisenbrey, Antoine Kichler, Burkhard Bechinger
The histidine-rich designer peptides of the LAH4 family exhibit potent antimicrobial, transfection, transduction and cell-penetrating properties. They form non-covalent complexes with their cargo, which often carry a negative overall charge at pH 7.4 and include a large range of molecules and structures such as oligonucleotides, including siRNA and DNA, peptides, proteins, nanodots and adeno-associated viruses. These complexes are thought to enter the cells through an endosomal pathway where the acidification of the organelle is essential for efficient endosomal escape...
January 9, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28055201/tumor-microenvironment-sensitive-liposomes-penetrate-tumor-tissue-via-attenuated-interaction-of-the-extracellular-matrix-and-tumor-cells-and-accompanying-actin-depolymerization
#9
Satoko Suzuki, Shoko Itakura, Ryo Matsui, Kayoko Nakayama, Takayuki Nishi, Akinori Nishimoto, Susumu Hama, Kentaro Kogure
Delivery of anticancer drugs into tumor cores comprised of malignant cancer cells can result in potent therapeutic effects. However, conventional nanoparticle-based drug delivery systems used for cancer therapy often exhibit inefficient tumor-penetrating properties, thus, suggesting the need to improve the functional design of such systems. Herein, we focus on the interactions between cancer cells and the extracellular matrix (ECM) and demonstrate that liposomes modified with slightly acidic pH-sensitive peptide (SAPSp-lipo) can penetrate in vivo tumor tissue and in vitro spheroids comprised of cancer cells and ECM...
January 19, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28054409/an-unexpected-cell-penetrating-peptide-from-bothrops-jararaca-venom-identified-through-a-novel-size-exclusion-chromatography-screening
#10
Juliana Mozer Sciani, Hugo Vigerelli, André Santos Costa, Diana Aparecida Dias Câmara, Paulo Luiz-de-Sá Junior, Daniel Carvalho Pimenta
Efficient drug delivery systems are currently one of the greatest challenges in pharmacokinetics, and the transposition of the gap between in vitro candidate molecule and in vivo test drug is, sometimes, poles apart. In this sense, the cell-penetrating peptides (CPP) may be the bridge uniting these worlds. Here, we describe a technique to rapidly identify unlabeled CPPs after incubation with liposomes, based on commercial desalting (size exclusion) columns and liquid chromatography-MS/MS, for peptide de novo sequencing...
January 5, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28052667/use-of-membrane-potential-to-achieve-transmembrane-modification-with-an-artificial-receptor
#11
Wataru Hatanaka, Miki Kawaguchi, Xizheng Sun, Yusuke Nagao, Hiroyuki Ohshima, Mitsuru Hashida, Yuriko Higuchi, Akihiro Kishimura, Yoshiki Katayama, Takeshi Mori
We developed a strategy to modify cell membranes with an artificial transmembrane receptor. Coulomb's force on the receptor, caused by the membrane potential, was used to achieve membrane penetration. A hydrophobically-modified cationic peptide was used as a membrane potential sensitive region, which was connected to biotin through a transmembrane oligoethylene glycol (OEG) chain. This artificial receptor gradually disappeared from the cell membrane via penetration, despite the presence of a hydrophilic OEG chain...
January 4, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28051846/selective-intracellular-delivery-of-ganglioside-gm3-binding-peptide-through-caveolae-raft-mediated-endocytosis
#12
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/28050849/glycin-rich-antimicrobial-peptide-yd1-from-b-amyloliquefaciens-induced-morphological-alteration-in-and-showed-affinity-for-plasmid-dna-of-e-coli
#13
Md Saifur Rahman, Yun Hee Choi, Yoon Seok Choi, Jin Cheol Yoo
Antimicrobial peptides (AMPs), low-molecular-weight proteins with broad-spectrum antimicrobial activity, are the most promising candidates for the development of novel antimicrobials. A powerful cationic glycine-rich AMP YD1 (MW ~ 1.0 kDa) was purified from Bacillus amyloliquefaciens CBSYD1 isolated from traditional Korean fermented food kimchi, for the treatment of multidrug-resistant (MDR) bacteria. Strain CBSYD1 was identified 99.79% similar to Bacillus amyloliquefaciens subsp. plantarum FZB42(T) by 16S rRNA sequence analysis...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28044164/a-peptide-functionalized-nanomotor-as-an-efficient-cell-penetrating-tool
#14
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/28041781/the-fountain-of-youth-by-targeting-senescent-cells
#15
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
December 20, 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28041565/the-fountain-of-youth-by-targeting-senescent-cells
#16
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28039053/novel-dock2-selective-inhibitory-peptide-that-suppresses-b-cell-line-migration
#17
Kotaro Sakamoto, Yusuke Adachi, Yusaku Komoike, Yusuke Kamada, Ryokichi Koyama, Yasunori Fukuda, Akito Kadotani, Taiji Asami, Jun-Ichi Sakamoto
Dedicator of cytokinesis 2 (DOCK2) is a key molecule for lymphocyte activation and migration. DOCK2 interacts with Ras-related C3 botulinus toxin substrate 1 (Rac1, GTPase) and mediates the GDP-GTP exchange reaction, indicating that inhibitors against protein-protein interaction (PPI) between DOCK2 and Rac1 would be good drug candidates for treating immune-related disorders. Here, we report DOCK2-selective PPI inhibitory peptides discovered using random peptide T7 phage display technology. These peptides inhibited DOCK2 activity at nanomolar concentrations and were delivered to intracellular compartments by combination with cell-penetrating peptide (CPP)...
December 27, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28035828/a-hepatic-carcinoma-selective-nucleic-acid-nanovector-assembled-by-endogenous-molecules-based-on-modular-strategy
#18
Fang Xie, Luchen Zhang, Jinliang Peng, Chong Li, Jun Pu, Yuhong Xu, Zixiu Du
We rationally formulated a nucleic acid nano-vector platform utilizing endogenous molecules in the following steps: nucleic acids are initially packed by a multifunctional peptide and a cationic liposome to form positively charged ternary complexes through electrostatic interaction; then the ternary complexes were coated with hyaluronic acid (HA) to form negatively charged quaternary nanocomplexes (Q-complexes). Among the components of Q-complexes, the multifunctional peptide was composed of a polysixteen-arginine (R16) and a hepatic tumor-targeted cell penetrating peptide (KRPTMRFRYTWNPMK); the cationic lipid component included DOTAP and fusogenic lipid DOPE; the HA component shielded the cationic ternary complexes and actively targeted the CD44 overexpressed on the surface of tumor cells...
December 30, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28035784/enhancing-the-cell-permeability-and-metabolic-stability-of-peptidyl-drugs-by-reversible-bicyclization
#19
Ziqing Qian, Curran A Rhodes, Lucas C McCroskey, Jin Wen, George Appiah-Kubi, David J Wang, Denis C Guttridge, Dehua Pei
Therapeutic applications of peptides are currently limited by their proteolytic instability and impermeability to the cell membrane. A general, reversible bicyclization strategy is now reported to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability...
December 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/28034616/enhancing-the-antimicrobial-activity-of-sus-scrofa-lysozyme-by-n-terminal-fusion-of-a-sextuple-unique-homologous-peptide
#20
Dewei Zhu, Guolin Cai, Xiaomin Li, Jian Lu, Liang Zhang
Sus scrofa lysozyme (SSL), an important component of the pig immune system, is a potential candidate to replace antibiotics in feed. However, there is little antimicrobial activity of natural SSL against gram-negative bacteria, which limits its application. In this study, a unique peptide (A-W-V-A-W-K) with antimicrobial activity against gram-negative bacteria was discovered and purified from trypsin hydrolysate of natural SSL. This unique peptide was fused to natural SSL and the recombinant fused SSL exhibited improved activity against gram-negative bacteria...
December 26, 2016: Journal of Biotechnology
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