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Cell penetrating peptide

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https://www.readbyqxmd.com/read/28338354/functional-oligopeptide-as-a-novel-strategy-for-drug-delivery
#1
Yujie Ji, Hongzhi Qiao, Jiayu He, Weidong Li, Rui Chen, Jingjing Wang, Li Wu, Rongfeng Hu, Jinao Duan, Zhipeng Chen
Oligopeptides, a type of short peptide, which consist of two to twenty amino acids, exhibit a variety of biological functions in drug delivery systems, such as specific targeting, cell penetration, self-assembled capacity and responsiveness to the environment. In this review, we aim to highlight the importance of functional oligopeptides for nanomedical applications and put forward the views on the future development direction of oligopeptide medicines. Oligopeptides have gained wide attentions due to their inherent properties, but the lack of understanding the mechanisms of in vivo transport behavior is the biggest problem and challenge at the present stage...
March 24, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28332260/biological-characterization-of-novel-nitroimidazole-peptide-conjugates-in-vitro-and-in-vivo
#2
Ralf Bergmann, Katrin Splith, Jens Pietzsch, Michael Bachmann, Ines Neundorf
Recently, we reported on the design of a multimodal peptide conjugate useful as delivery platform for targeting hypoxic cells. A nitroimidazole (2-(2-nitroimidazol-1-yl)acetic acid, NIA) moiety, which is selectively entrapped in hypoxic cells, was coupled to a cell-penetrating peptide serving as the transporter. Furthermore, attachment of a bifunctional linker allowed the introduction of a diagnostic or therapeutic radiometal. However, although selective tumor accumulation could be detected in vivo, a fast renal clearance of the compound was observed...
March 23, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28322369/the-fusogenic-peptide-ha2-impairs-selectivity-of-cxcr4-targeted-protein-nanoparticles
#3
L Sánchez-García, N Serna, M Mattanovich, P Cazzanelli, A Sánchez-Chardi, O Conchillo-Solé, F Cortés, X Daura, U Unzueta, R Mangues, A Villaverde, E Vázquez
We demonstrate here that the genetic incorporation of the fusogenic peptide HA2 into a CXCR4-targeted protein nanoparticle dramatically reduces the specificity of the interaction between nanoparticles and cell receptors, a factor to be considered when designing tumor-homing drug vehicles displaying endosomal-escape agents. The loss of specificity is concomitant with enhanced cell penetrability.
March 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28321253/trends-in-the-binding-of-cell-penetrating-peptides-to-sirna-a-molecular-docking-study
#4
P V G M Rathnayake, B G C M Gunathunge, P N Wimalasiri, D N Karunaratne, R J K U Ranatunga
The use of gene therapeutics, including short interfering RNA (siRNA), is limited by the lack of efficient delivery systems. An appealing approach to deliver gene therapeutics involves noncovalent complexation with cell penetrating peptides (CPPs) which are able to penetrate the cell membranes of mammals. Although a number of CPPs have been discovered, our understanding of their complexation and translocation of siRNA is as yet insufficient. Here, we report on computational studies comparing the binding affinities of CPPs with siRNA, considering a variety of CPPs...
2017: Journal of Biophysics
https://www.readbyqxmd.com/read/28314993/comparative-analysis-of-internalisation-haemolytic-cytotoxic-and-antibacterial-effect-of-membrane-active-cationic-peptides-aspects-of-experimental-setup
#5
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/28299853/the-effect-of-a-beta-lactamase-inhibitor-peptide-on-bacterial-membrane-structure-and-integrity-a-comparative-study
#6
Begum Alaybeyoglu, Bilge Gedik Uluocak, Berna Sariyar Akbulut, Elif Ozkirimli
Co-administration of beta-lactam antibiotics and beta-lactamase inhibitors has been a favored treatment strategy against beta-lactamase-mediated bacterial antibiotic resistance, but the emergence of beta-lactamases resistant to current inhibitors necessitates the discovery of novel non-beta-lactam inhibitors. Peptides derived from the Ala46-Tyr51 region of the beta-lactamase inhibitor protein are considered as potent inhibitors of beta-lactamase; unfortunately, peptide delivery into the cell limits their potential...
March 16, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28296562/immunomodulatory-yersinia-outer-proteins-yops-useful-tools-for-bacteria-and-humans-alike
#7
Benjamin Grabowski, M Alexander Schmidt, Christian Rüter
Human-pathogenic Yersinia produce plasmid-encoded Yersinia outer proteins (Yops), which are necessary to down-regulate anti-bacterial responses that constrict bacterial survival in the host. These Yops are effectively translocated directly from the bacterial into the target cell cytosol by the type III secretion system (T3SS). Cell-penetrating peptides (CPPs) in contrast are characterized by their ability to autonomously cross cell membranes and to transport cargo - independent of additional translocation systems...
March 15, 2017: Virulence
https://www.readbyqxmd.com/read/28296169/pyrrole-based-macrocyclic-small-molecule-inhibitors-targeting-oocyte-maturation
#8
Jeong Kyu Bang, Pethaiah Gunasekaran, So Rim Lee, Seung-Min Jeong, Jeong-Woo Kwon, Toshiki Takei, Yuya Asahina, Geul Bang, Seongnyeon Kim, Mija Ahn, Eun Kyung Ryu, Hak Nam Kim, Ki-Yub Nam, Song Yub Shin, Hironobu Hojo, Suk Namgoong, Nam-Hyung Kim
Polo-like kinase 1 (PLK1) plays crucial roles in various stages of oocyte maturation. Recently, we reported that the peptidomimetic AB103-8 that targets polo box domain (PBD) of PLK1 affected oocyte meiotic maturation and meiosis resumption. However, to overcome the peptidic drawbacks, we designed and synthesized a series of pyrrole-based small-molecule inhibitors and screened against porcine oocyte maturation rates. Among them, compound 4 showed the highest inhibitory activity with enhanced inhibition against the embryos blastocyst formation...
March 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28291364/multifunctional-nanoparticles-loading-with-docetaxel-and-gdc0941-for-reversing-multidrug-resistance-mediated-by-pi3k-akt-signal-pathway
#9
Yiyue Wang, Jing Li, Jing Jing Chen, Xuan Gao, Zun Huang, Qi Shen
The polylactic-co-glycolic acid polyethylene glycol conjugated with cell penetrating peptide R7 (PLGA-PEG-R7)/polysulfadimethoxine-folate nanoparticles loaded with docetaxel (DTX) and GDC0941 (R7/PSD-Fol NPs) were prepared to overcome multidrug resistance (MDR) and enhance the antitumor activity. First, polysulfadimethoxine-folate was synthesized to construct the R7/PSD-Fol NPs. The R7/PSD-Fol NPs were prepared with the abilities of effective entrapment and drug loading. Due to the pH-sensitive effect of PSD-folate, the releasing of DTX and GDC0941 from the R7/PSD-Fol NPs was lower in pH 7...
March 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28290666/taming-the-wildness-of-trojan-horse-peptides-by-charge-guided-masking-and-protease-triggered-demasking-for-the-controlled-delivery-of-antitumor-agents
#10
Nian-Qiu Shi, Xian-Rong Qi
Cell-penetrating peptide (CPP), also called "Trojan Horse" peptide, has become a successful approach to deliver various payloads into cells for achieving the intracellular access. However, the "Trojan Horse" peptide is too wild, not just to "Troy", but rather widely distributed in the body. Thus, there is an urgent need to tame the wildness of "Trojan Horse" peptide for targeted delivery of antineoplastic agents to the tumor site. To achieve this goal, we exploit a masked CPP-doxorubicin conjugate platform for targeted delivery of chemotherapeutic drugs using charge-guided masking and protease-triggered demasking strategies...
March 14, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28289371/exosomes-origins-and-therapeutic-potential-for-neurodegenerative-disease
#11
REVIEW
Diana K Sarko, Cindy E McKinney
Exosomes, small lipid bilayer vesicles, are part of the transportable cell secretome that can be taken up by nearby recipient cells or can travel through the bloodstream to cells in distant organs. Selected cellular cytoplasm containing proteins, RNAs, and other macromolecules is packaged into secreted exosomes. This cargo has the potential to affect cellular function in either healthy or pathological ways. Exosomal content has been increasingly shown to assist in promoting pathways of neurodegeneration such as β-amyloid peptide (Aβ) accumulation forming amyloid plaques in the brains of patients with Alzheimer's disease, and pathological aggregates of proteins containing α-synuclein in Parkinson's disease transferred to the central nervous system via exosomes...
2017: Frontiers in Neuroscience
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
#12
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
#13
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/28284862/investigation-on-cellular-uptake-and-pharmacodynamics-of-dock2-inhibitory-peptides-conjugated-with-cell-penetrating-peptides
#14
Yusuke Adachi, Kotaro Sakamoto, Tadashi Umemoto, Yasunori Fukuda, Akiyoshi Tani, Taiji Asami
Protein-protein interaction between dedicator of cytokinesis 2 (DOCK2) and Ras-related C3 botulinum toxin substrate 1 (Rac1) is an attractive intracellular target for transplant rejection and inflammatory diseases. Recently, DOCK2-selective inhibitory peptides have been discovered, and conjugation with oligoarginine cell-penetrating peptide (CPP) improved inhibitory activity in a cell migration assay. Although a number of CPPs have been reported, oligoarginine was only one example introduced to the inhibitory peptides...
February 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28282450/secretory-proteins-are-delivered-to-the-septin-organized-penetration-interface-during-root-infection-by-verticillium-dahliae
#15
Ting-Ting Zhou, Yun-Long Zhao, Hui-Shan Guo
Successful infection of the host requires secretion of effector proteins to evade or suppress plant immunity. Secretion of effectors in root-infecting fungal pathogens, however, remains unexplored. We previously reported that Verticillium dahliae, a root-infecting phytopathogenic fungus, develops a penetration peg from a hyphopodium to infect cotton roots. In this study, we report that a septin ring, requiring VdSep5, partitions the hyphopodium and the invasive hypha and form the specialized fungus-host interface...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28279738/modifying-plasmid-loaded-hsa-nanoparticles-with-cell-penetrating-peptides-cellular-uptake-and-enhanced-gene-delivery
#16
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/28277671/enzyme-cleavable-polymeric-micelles-for-the-intracellular-de-livery-of-pro-apoptotic-peptides
#17
Hanna B Kern, Selvi Srinivasan, Anthony J Convertine, David Hockenbery, Oliver W Press, Patrick S Stayton
Peptides derived from the third Bcl-2 homology domain (BH3) renormalize apoptotic signaling by antagonizing pro-survival Bcl-2 family members. They serve as a model for potential peptide drugs that possess therapeutic activities but are limited by delivery barriers including short circulation half-lives and poor penetration into cells. A diblock polymeric micelle carrier for the BIM BH3 peptide was recently described that demonstrated anti-tumor activity in a B-cell lymphoma xenograft model [Berguig et al., Mol Ther, 2015]...
March 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28277548/optimized-labeling-of-membrane-proteins-for-applications-to-super-resolution-imaging-in-confined-cellular-environments-using-monomeric-streptavidin
#18
Ingrid Chamma, Olivier Rossier, Grégory Giannone, Olivier Thoumine, Matthieu Sainlos
Recent progress in super-resolution imaging (SRI) has created a strong need to improve protein labeling with probes of small size that minimize the target-to-label distance, increase labeling density, and efficiently penetrate thick biological tissues. This protocol describes a method for labeling genetically modified proteins incorporating a small biotin acceptor peptide with a 3-nm fluorescent probe, monomeric streptavidin. We show how to express, purify, and conjugate the probe to organic dyes with different fluorescent properties, and how to label selectively biotinylated membrane proteins for SRI techniques (point accumulation in nanoscale topography (PAINT), stimulated emission depletion (STED), stochastic optical reconstruction microscopy (STORM))...
April 2017: Nature Protocols
https://www.readbyqxmd.com/read/28276242/cellular-uptake-mechanism-of-cationic-branched-polypeptides-with-poly-l-lys-backbone
#19
Rita Szabó, Mónika Sebestyén, György Kóczán, Ádám Orosz, Gábor Mező, Ferenc Hudecz
Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study, we report our findings on the cellular uptake characteristics of nine structurally related polylysine-based polypeptides with cationic side chains composed of (i) single amino acid (poly[Lys(Xi)], XiK) or (ii) oligo[dl-alanine] (poly[Lys(dl-Alam)], AK) or (iii) oligo[dl-alanine] with an additional amino acid (X) at the terminal position (poly[Lys(Xi-dl-Alam)] (XAK)) or (iv) at the position next to the polylysine backbone (poly[Lys(dl-Alam-Xi)] (AXK))...
March 9, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28275774/antibiotic-gold-tethering-of-antimicrobial-peptides-to-gold-nanoparticles-maintains-conformational-flexibility-of-peptides-and-improves-trypsin-susceptibility
#20
Parvesh Wadhwani, Nico Heidenreich, Benjamin Podeyn, Jochen Bürck, Anne S Ulrich
Peptide-coated nanoparticles are valuable tools for diverse biological applications, such as drug delivery, molecular recognition, and antimicrobial action. The functionalization of pre-fabricated nanoparticles with free peptides in solution is inefficient either due to aggregation of the particles or due to the poor ligand exchange reaction. Here, we present a one-pot synthesis for preparing gold nanoparticles with a homogeneous distribution that are covered in situ with cationic peptides in a site-selective manner via Cys-residue at the N-terminus...
March 9, 2017: Biomaterials Science
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