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Cell penetrating peptide

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https://www.readbyqxmd.com/read/29332035/an-aspartyl-cathepsin-targeted-pet-agent-application-in-an-alzheimer-s-disease-mouse-model
#1
Jonatan A Snir, Mojmir Suchy, Geron A Bindseil, Michael Kovacs, Blaine A Chronik, Robert H E Hudson, Stephen H Pasternak, Robert Bartha
BACKGROUND: Early detection of Alzheimer's disease (AD) pathology is a serious challenge for both diagnosis and clinical trials. The aspartyl protease, Cathepsin D (CatD), is overexpressed in AD and could be a biomarker of disease. We have previously designed a unique contrast agent (CA) for dual-optical and magnetic resonance imaging of the activity of the CatD class of enzymes. OBJECTIVE: To compare the uptake and retention of a novel, more sensitive, and clinically-translatable 68Ga PET tracer targeting CatD activity in 5XFAD mice and non-Tg littermates...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29329747/antibacterial-properties-of-latarcin-1-derived-cell-penetrating-peptides
#2
Deepthi Poornima Budagavi, Archana Chugh
Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) share certain physicochemical parameters such as amphipathicity, hydrophobicity, cationicity and pI, due to which these two groups of peptides also exhibit overlapping functional characteristics. In our current work, we have evaluated antimicrobial properties of cell-penetrating peptides derived from Latarcin1. Latarcin derived peptide (LDP) exhibited antimicrobial activity against representative microorganisms tested and bactericidal effect against methicillin resistant Staphylococcus aureus (MRSA), which was used as model organism of study in the present work...
January 9, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29329001/improved-antibacterial-activity-of-a-marine-peptide-n2-against-intracellular-salmonella-typhimurium-by-conjugating-with-cell-penetrating-peptides-blfcin6-tat11
#3
Zhanzhan Li, Xiao Wang, Da Teng, Ruoyu Mao, Ya Hao, Na Yang, Huixian Chen, Xiumin Wang, Jianhua Wang
Salmonellae, gram-negative bacteria, are facultative intracellular pathogens that cause a number of diseases in animals and humans. The poor penetration ability of antimicrobial agents limits their use in the treatment of intracellular bacterial infections. In this study, the cell-penetrating peptides (CPPs) bLFcin6 and Tat11 were separately conjugated to the antimicrobial peptide N2, and the antibacterial activity and pharmacodynamics of the CPPs-N2 conjugates were first evaluated against Salmonellae typhimurium in vitro and in macrophage cells...
December 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#4
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29327008/an-upconversion-nanoparticle-based-fluorescence-resonance-energy-transfer-system-for-effectively-sensing-caspase-3-activity
#5
Lin Liu, Hua Zhang, Daqian Song, Zhenxin Wang
We report a new fluorescence resonance energy transfer (FRET) sensing platform for the sensitive detection of caspase-3 activity in vitro and in cells using NaGdF4:Yb3+,Er3+@NaGdF4 upconversion nanoparticles (UCNPs) as the energy donor and Rhodamine B (RB) as the energy acceptor. The phosphorylated RB-modified peptide containing a caspase-3 cleavage site and cell-penetrating peptide (CPP) motif (sequence, (RB)-DEVDGGS(p)GCGT(p)GRKKRRQRRRPQ) is immobilized on the UCNP surface via the strong coordination interaction between Gd3+ ions with phosphate...
January 12, 2018: Analyst
https://www.readbyqxmd.com/read/29317198/rhodomyrtone-rom-is-a-membrane-active-compound
#6
Jongkon Saising, Minh Thu Nguyen, Thomas Härtner, Patrick Ebner, Abdulla Al Mamun Bhuyan, Anne Berscheid, Melanie Muehlenkamp, Sina Schäkermann, Nimerta Kumari, Martin E Maier, Supayang P Voravuthikunchai, Julia Bandow, Florian Lang, Heike Brötz-Oesterhelt, Friedrich Götz
Particularly in Asia medicinal plants with antimicrobial activity are used for therapeutic purpose. One such plant-derived antibiotic is rhodomyrtone (Rom) isolated from Rhodomyrtus tomentosa leaves. Rom shows high antibacterial activity against a wide range of Gram-positive bacteria, however, its mode of action is still unclear. Reporter gene assays and proteomic profiling experiments in Bacillus subtilis indicate that Rom does not address classical antibiotic targets like translation, transcription or DNA replication, but acts at the cytoplasmic membrane...
January 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29316746/vegf-sirna-delivery-by-a-cancer-specific-cell-penetrating-peptide
#7
Young Woong Lee, Young Eun Hwang, Ju Young Lee, Jung-Hoon Sohn, Bong Hyun Sung, Sun Chang Kim
RNA interference provides an effective tool for developing antitumor therapies. Cell-penetrating peptides (CPPs) are delivery vectors widely used to efficiently transport small-interfering RNA (siRNA) to intracellular targets. In this study, we investigated the efficacy of the cancer-specific CPP carrier BR2 to specifically transport siRNA to cancer-target cells. Our results showed that BR2 formed a complex with anti-vascular endothelial growth factor siRNA (siVEGF) that exhibited the appropriate size and surface charge for in vivo treatment...
January 11, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29315863/activatable-protein-nanoparticles-for-targeted-delivery-of-therapeutic-peptides
#8
Xi Yu, Xingchun Gou, Peng Wu, Liang Han, Daofeng Tian, Fengyi Du, Zeming Chen, Fuyao Liu, Gang Deng, Ann T Chen, Chao Ma, Jun Liu, Sara M Hashmi, Xing Guo, Xiaolong Wang, Haitian Zhao, Xinran Liu, Xudong Zhu, Kevin Sheth, Qianxue Chen, Louzhen Fan, Jiangbing Zhou
Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self-assembly of three independent polypeptides based on pairwise coiled-coil dimerization...
January 8, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29315333/cell-penetrating-peptide-driven-cre-recombination-in-porcine-primary-cells-and-generation-of-marker-free-pigs
#9
Qianqian Kang, Zhaolin Sun, Zhiyuan Zou, Ming Wang, Qiuyan Li, Xiaoxiang Hu, Ning Li
Cell-penetrating peptides (CPPs) have been increasingly used to deliver various molecules, both in vitro and in vivo. However, there are no reports of CPPs being used in porcine fetal fibroblasts (PFFs). The increased use of transgenic pigs for basic research and biomedical applications depends on the availability of technologies for efficient genetic-modification of PFFs. Here, we report that three CPPs (CPP5, TAT, and R9) can efficiently deliver active Cre recombinase protein into PFFs via an energy-dependent endocytosis pathway...
2018: PloS One
https://www.readbyqxmd.com/read/29309722/a-cell-permeable-stapled-peptide-inhibitor-of-the-estrogen-receptor-coactivator-interaction
#10
Thomas E Speltz, Jeanne M Danes, Joshua D Stender, Jonna Frasor, Terry W Moore
We and others have proposed that coactivator binding inhibitors, which block the interaction of estrogen receptor and steroid receptor coactivators, may represent a potential class of new breast cancer therapeutics. The development of coactivator binding inhibitors has been limited, however, because many of the current molecules which are active in in vitro and biochemical assays are not active in cell-based assays. Our goal in this work was to prepare a coactivator binding inhibitor active in cellular models of breast cancer...
January 8, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29307194/synthesis-characterization-and-evaluation-of-triptolide-cell-penetrating-peptide-derivative-for-transdermal-delivery-of-triptolide
#11
Tian Tian, Yuming Song, Ke Li, Yuming Sun, Qing Wang
Triptolide (TP) has been used as one of the most common systemic treatments for various diseases since 1960s. However, TP displays diverse side effects on various organs which limits its clinical application. To overcome this issue, numerous C-14 hydroxyl group derivatives of TP have been synthesized. In this research, the C-14 hydroxyl group of TP is modified by a cell penetrating peptide poly arginine (R7). The derivative TP-disulfide-CR7 (TP-S-S-CR7) containing a disulfide linkage between TP and R7 possesses less toxicity at various concentrations on immortal human keratinocyte line (HaCaT) cell line by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay compared with free TP...
January 8, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29304437/peptide-targeted-stimuli-responsive-polymersomes-for-delivering-a-cancer-stemness-inhibitor-to-cancer-stem-cell-microtumors
#12
Fataneh Karandish, James Froberg, Pawel Borowicz, John C Wilkinson, Yongki Choi, Sanku Mallik
Often cancer relapses after an initial response to chemotherapy because of the tumor's heterogeneity and the presence of progenitor stem cells, which can renew. To overcome drug resistance, metastasis, and relapse in cancer, a promising approach is the inhibition of cancer stemness. In this study, the expression of the neuropilin-1 receptor in both pancreatic and prostate cancer stem cells was identified and targeted with a stimuli-responsive, polymeric nanocarrier to deliver a stemness inhibitor (napabucasin) to cancer stem cells...
December 24, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29303375/structure-optimization-to-improve-the-delivery-efficiency-and-cell-selectivity-of-a-tumor-targeting-cell-penetrating-peptide
#13
Xue-Wei Cao, Xu-Zhong Yang, Xuan Du, Long-Yun Fu, Tao-Zhu Zhang, Han-Wen Shan, Jian Zhao, Fu-Jun Wang
Cell-penetrating peptide (CPP) is used for the delivery of biomacromolecules across the cell membrane and is limited in cancer therapy due to the lack of cell selectivity. Epidermal growth factor receptor (EGFR) has been widely used in clinical targeted therapy for tumors. Here we reported a novel tumor targeting cell-penetrating peptide (TCPP), EHB (ELBD-C6H) with 20-fold and 3000-fold greater transmembrane ability and tumor cell selectivity than our previously reported S3-HBD and classic CPP TAT, respectively...
January 5, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29299557/investigation-of-the-interaction-of-amyloid-%C3%AE-peptide-11-42-oligomers-with-a-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine-popc-membrane-using-molecular-dynamics-simulation
#14
Ning Xiang, Yuan Lyu, Xiao Zhu, Ganesan Narsimhan
Some amyloid related proteins/peptides are involved in aggregation and pore formation in phospholipid membranes (cell membranes), which result in a variety of neurological disorders such as Alzheimer's disease, Parkinson's disease and Huntington disease. In this research, the mechanism of pore formation by β amyloid (Aβ) peptides was investigated using molecular dynamics simulation by simulating the interaction of the Aβ(11-42) peptide, with a lipid membrane and the potential of the mean force of interaction was evaluated...
January 4, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29298891/cleavage-of-the-c-terminal-fragment-of-reovirus-%C3%AE-1-is-required-for-optimal-infectivity
#15
Anthony J Snyder, Pranav Danthi
The mammalian orthoreovirus (reovirus) outer capsid, which is composed of 200 μ1/σ3 heterohexamers and a maximum of 12 σ1 trimers, contains all of the proteins that are necessary for attaching to and entering host cells. Following attachment, reovirus is internalized by receptor-mediated endocytosis and acid-dependent cathepsin proteases degrade the σ3 protein. This process generates a metastable intermediate, called infectious subviral particle (ISVP), in which the μ1 membrane penetration protein is exposed...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29297759/nuclear-targeting-peptide-modified-dox-loaded-phbv-nanoparticles-enhance-drug-efficacy-by-targeting-to-saos-2-cell-nuclear-membranes
#16
Ayla Şahin, Gozde Eke, Arda Buyuksungur, Nesrin Hasirci, Vasif Hasirci
The aim of this study was to target nano sized (266±25 nm diameter) poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) particles carrying Doxorubicin (DOX), an anticancer agent, to human osteosarcoma cells (Saos-2). A nuclear targeting molecule (Nuclear Localization Signal, NLS), a 17 a.a. peptide, was attached onto the doxorubicin loaded nanoparticles. NLS conjugated nanoparticles surrounded the cell nuclei, but did not penetrate them. Free and nanoparticle-loaded doxorubicin entered the cytoplasm but were evenly distributed within the cytoplasm...
January 3, 2018: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/29290826/a-cell-penetrating-whole-molecule-antibody-targeting-intracellular-hbx-suppresses-hepatitis-b-virus-via-trim21-dependent-pathway
#17
Jun-Fang Zhang, Hua-Long Xiong, Jia-Li Cao, Shao-Juan Wang, Xue-Ran Guo, Bi-Yun Lin, Ying Zhang, Jing-Hua Zhao, Ying-Bin Wang, Tian-Ying Zhang, Quan Yuan, Jun Zhang, Ning-Shao Xia
Rationale: Monoclonal antibodies (mAbs) mostly targeting extracellular or cell surface molecules have been widely used in the treatment of various diseases. However, mAbs cannot pass through the cell membrane as efficiently as small compounds, thus limiting their use against intracellular targets. Methods to shuttle antibodies into living cells may largely expand research and application in areas based on mAbs. Hepatitis B virus X protein (HBx) is an important intracellular multi-functional viral protein in the life cycle of hepatitis B virus (HBV)...
2018: Theranostics
https://www.readbyqxmd.com/read/29290795/tumor-penetrating-peptide-conjugated-and-doxorubicin-loaded-t1-t2-dual-mode-mri-contrast-agents-nanoparticles-for-tumor-theranostics
#18
Lipeng Gao, Jing Yu, Yang Liu, Jinge Zhou, Lei Sun, Jing Wang, Jianzhong Zhu, Hui Peng, Weiyue Lu, Lei Yu, Zhiqiang Yan, Yiting Wang
The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. Methods: In this study, a tumor-penetrating peptide RGERPPR (RGE) modified, Gd-DTPA conjugated, and doxorubicin (DOX) loaded Fe3O4@SiO2@mSiO2 nanoparticle drug delivery system (Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs) was prepared for tumor theranostics. Results: The Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs showed a z-average hydrodynamic diameter of about 90 nm, and a pH-sensitive DOX release profile...
2018: Theranostics
https://www.readbyqxmd.com/read/29288282/promotion-of-sh-sy5y-cell-growth-by-gold-nanoparticles-modified-with-6-mercaptopurine-and-a-neuron-penetrating-peptide
#19
Yaruo Xiao, Enqi Zhang, Ailing Fu
Much effort has been devoted to the discovery of effective biomaterials for nerve regeneration. Here, we reported a novel application of gold nanoparticles (AuNPs) modified with 6-mercaptopurine (6MP) and a neuron-penetrating peptide (RDP) as a neurophic agent to promote proliferation and neurite growth of human neuroblastoma (SH-SY5Y) cells. When the cells were treated with 6MP-AuNPs-RDP conjugates, they showed higher metabolic activity than the control. Moreover, SH-SY5Y cells were transplanted onto the surface coated with 6MP-AuNPs-RDP to examine the effect of neurite development...
December 29, 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/29287907/nir-induced-spatiotemporally-controlled-gene-silencing-by-upconversion-nanoparticle-based-sirna-nanocarrier
#20
Guojun Chen, Ben Ma, Ruosen Xie, Yuyuan Wang, Kefeng Dou, Shaoqin Gong
Spatiotemporal control over the release or activation of biomacromolecules such as siRNA remains a significant challenge. Light-controlled release has gained popularity in recent years; however, a major limitation is that most photoactivable compounds/systems respond only to UV irradiation, but not near-infrared (NIR) light that offers a deeper tissue penetration depth and better biocompatibility. This paper reports a simple NIR-to-UV upconversion nanoparticle (UCNP)-based siRNA nanocarrier for NIR-controlled gene silencing...
December 26, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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