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Cell-penetrating peptide

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https://www.readbyqxmd.com/read/29780514/construction-of-histidine-containing-hydrocarbon-stapled-cell-penetrating-peptides-for-in-vitro-and-in-vivo-delivery-of-sirnas
#1
Soonsil Hyun, Yoonhwa Choi, Ha Neul Lee, Changki Lee, Donghoon Oh, Dong-Ki Lee, Changjin Lee, Yan Lee, Jaehoon Yu
A hydrocarbon stapled peptide based strategy was used to develop an optimized cell penetrating peptide for siRNA delivery. Various stapled peptides, having amphipathic Leu- and Lys-rich regions, were prepared and their cell penetrating potentials were evaluated. One peptide, stEK, was found to have high cell penetration and siRNA delivery abilities at low nanomolar concentrations. In order to improve its ability to promote gene silencing, stEK was modified by replacing several Lys residues with His moieties...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780163/heteromerization-of-%C3%AE-opioid-receptor-and-cholecystokinin-b-receptor-through-the-third-transmembrane-domain-of-the-%C3%AE-opioid-receptor-contributes-to-the-anti-opioid-effects-of-cholecystokinin-octapeptide
#2
Yin Yang, Qian Li, Qi-Hua He, Ji-Sheng Han, Li Su, You Wan
Activation of the cholecystokinin type B receptor (CCKBR) by cholecystokinin octapeptide (CCK-8) inhibits opioid analgesia. Chronic opiate treatment leads to an increase in the CCK-8 concentration and thus enhances the antagonism of CCK-8 against opioid analgesia; the underlying molecular mechanisms remain of great interest. In the present study, we validated the colocalization of the μ-opioid receptor (MOR) and CCKBR in pain signal transmission-related spinal cord dorsal horn and dorsal root ganglion neurons of rats...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29777875/switching-cell-penetrating-and-cxcr4-binding-activities-of-nanoscale-organized-arginine-rich-peptides
#3
Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde
Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown...
May 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29774608/virion-like-membrane-breaking-nanoparticles-with-tumor-activated-cell-and-tissue-dual-penetration-conquer-impermeable-cancer
#4
Xiao Zhang, Xianghui Xu, Yachao Li, Cheng Hu, Zhijun Zhang, Zhongwei Gu
Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion-like membrane-breaking nanoparticles (MBNs) to smoothly accomplish tumor-activated cell-and-tissue dual-penetration for surmounting impermeable drug-resistant cancer. Tailor-made dendritic arginine-rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self-assemble into virion-like nanoparticles in aqueous solution, having highly ordered secondary structure...
May 17, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29770868/effect-of-dimerized-melittin-on-gastric-cancer-cells-and-antibacterial-activity
#5
Elaheh Jamasbi, Sasidharan S Lucky, Wenyi Li, Mohammed Akhter Hossain, Ponnampalam Gopalakrishnakone, Frances Separovic
Melittin is the peptide toxin found in bee venom and is effective against cancer cells. To enhance its activity, a branched dimeric form of melittin was designed. The monomeric form of the peptide was more cytotoxic against gastric cancer cells at low concentrations (1-5 μM) than the dimer form, while the cytotoxic effect was comparable at higher concentrations (10 μM). Confocal microscopy showed that both the monomer and dimer forms of melittin with fluorescent label at the C terminus penetrated the cytoplasm and localized at the cell nucleus and disrupted the cell membrane...
May 16, 2018: Amino Acids
https://www.readbyqxmd.com/read/29769639/a-novel-cell-penetrating-peptide-protects-against-neuron-apoptosis-after-cerebral-ischemia-by-inhibiting-the-nuclear-translocation-of-annexin-a1
#6
Xing Li, Lu Zheng, Qian Xia, Lu Liu, Meng Mao, Huijuan Zhou, Yin Zhao, Jing Shi
Nuclear translocation of annexin A1 (ANXA1) has recently been reported to participate in neuronal apoptosis after cerebral ischemia. Prevention of the nuclear translocation of ANXA1 should therefore inhibit neuronal apoptosis and protect against cerebral stroke. Here, we found that, in the repeat III domain of ANXA1, the amino-acid residues from R228 to F237 function as a unique nuclear translocation signal (NTS) and are required for nuclear translocation of ANXA1. Intriguingly, we synthesized a cell-penetrating peptide derived by conjugating the trans-activator of transcription (Tat) domain to the NTS sequence...
May 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29767957/magnetic-manipulation-of-reversible-nanocaging-controls-in-vivo-adhesion-and-polarization-of-macrophages
#7
Heemin Kang, Hee Joon Jung, Sung Kyu Kim, Dexter Siu Hong Wong, Sien Lin, Gang Li, Vinayak P Dravid, Liming Bian
Macrophages are key immune cells that perform various physiological functions, such as the maintenance of homeostasis, host defense, disease progression, and tissue regeneration. Macrophages adopt distinctly polarized phenotypes, such as pro-inflammatory M1 phenotype or anti-inflammatory (pro-healing) M2 phenotype, to execute disparate functions. The remotely controlled reversible uncaging of bioactive ligands, such as Arg-Gly-Asp (RGD) peptide, is an appealing approach for temporally regulating the adhesion and resultant polarization of macrophages on the implants in vivo...
May 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29764120/multi-arm-nanoconjugates-for-cancer-cell-targeted-delivery-of-photosensitizers
#8
Yan Zhao, Fang Li, Chengqiong Mao, Xin Ming
Photodynamic therapy, a procedure that uses a photosensitizer to enable light therapy selectively at diseased sites, remains underutilized in oncological clinic. To further improve its cancer selectivity, we developed a polymeric nanosystem by conjugating a photosensitizer IRDye 700DX (IR700) and cancer targeting RGD peptide to 8-arm polyethylene glycol (PEG). The resulting nanoconjugates (RGD-8PEG-IR700) exhibited a hydrodynamic size of 6.6 nm with narrow distribution of size. The targeted nanoconjugates showed significantly higher intracellular uptake of IR700 in integrin αvβ3-expressing A375 and SKOV3 cells when compared with non-targeted control 8PEG-IR700, and excess amount of RGD peptides could abolish this enhancement, indicating a receptor-medicated uptake mechanism for the targeted polymer conjugates...
May 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29763715/near-infrared-light-activated-red-emitting-upconverting-nanoplatform-for-t-1-weighted-magnetic-resonance-imaging-and-photodynamic-therapy
#9
Xiang-Long Tang, Jun Wu, Ben-Lan Lin, Sheng Cui, Hong-Mei Liu, Ru-Tong Yu, Xiao-Dong Shen, Ting-Wei Wang, Wei Xia
Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4 : 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+ , is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs...
May 12, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29762718/cell-penetrating-thiazole-peptides-inhibit-c-myc-expression-via-site-specific-targeting-of-c-myc-g-quadruplex
#10
Debasish Dutta, Manish Debnath, Diana Müller, Rakesh Paul, Tania Das, Irene Bessi, Harald Schwalbe, Jyotirmayee Dash
The structural differences among different G-quadruplexes provide an opportunity for site-specific targeting of a particular G-quadruplex structure. However, majority of G-quadruplex ligands described thus far show little selectivity among different G-quadruplexes. In this work, we delineate the design and synthesis of a crescent-shaped thiazole peptide that preferentially stabilizes c-MYC quadruplex over other promoter G-quadruplexes and inhibits c-MYC oncogene expression. Biophysical analysis such as Förster resonance energy transfer (FRET) melting and fluorescence spectroscopy show that the thiazole peptide TH3 can selectively interact with the c-MYC G-quadruplex over other investigated G-quadruplexes and duplex DNA...
May 14, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29757394/a-barley-powdery-mildew-fungus-non-autonomous-retrotransposon-encodes-a-peptide-that-supports-penetration-success-on-barley
#11
Mathias Nottensteiner, Bernd Zechmann, Christopher McCollum, Ralph Hückelhoven
Pathogens overcome plant immunity by the means of secreted effectors. Host effector targets often act in pathogen defense but might also support fungal accommodation or nutrition. The barley ROP GTPase HvRACB is involved in accommodation of fungal haustoria of the powdery mildew fungus Blumeria graminis f.sp. hordei (Bgh) in barley epidermal cells. We found that HvRACB interacts with the ROP-interactive peptide 1 (ROPIP1) that is encoded on the active non-long terminal repeat retroelement Eg-R1 of Bgh. Over-expression of ROPIP1 in barley epidermal cells and host-induced post-transcriptional gene silencing (HIGS) of ROPIP1 suggested that ROPIP1 is involved in virulence of Bgh...
May 11, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29757340/polyethylene-glycol-and-octa-arginine-dual-functionalized-nanographene-oxide-an-optimization-for-efficient-nucleic-acid-delivery
#12
Rana Imani, Satya Prakash, Hojatollah Vali, Shahab Faghihi
The successful application of nucleic acid-based therapy for the treatment of various cancers is largely dependent on a safe and efficient delivery system. A dual-functionalized graphene oxide (GO)-based nanocarrier with the conjugation of aminated-polyethylene glycol (PEG-diamine) and octa-arginine (R8) for the intracellular delivery of nucleic acids is proposed. The functionalized sites are covalently co-conjugated and the PEG : R8 molar ratio is optimized at 10 : 1 to achieve a hydrocolloidally stable size of 252 ± 2...
May 14, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29747160/targeting-liver-cancer-and-associated-pathologies-in-mice-with-a-mitochondrial-vdac1-based-peptide
#13
Srinivas Pittala, Yakov Krelin, Varda Shoshan-Barmatz
Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. Despite progress in identifying risk factors, the incidence of HCC is increasing. Moreover, therapeutic options are limited and survival is poor. Therefore, alternative and innovative therapeutic strategies are urgently required. R-Tf-D-LP4, a cell-penetrating peptide derived from the mitochondrial multifunctional protein the voltage-dependent anion channel (VDAC1), is identified here as a highly effective liver cancer treatment. Recently, we demonstrated that R-Tf-D-LP4 induced apoptosis and inhibited tumor growth in mouse models...
May 7, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29746864/drug-delivery-using-polyhistidine-peptide-modified-liposomes-that-target-the-endogenous-lysosome
#14
Taiki Hayashi, Matsumi Shinagawa, Tsuyoshi Kawano, Takashi Iwasaki
Cell-penetrating peptides (CPPs) can deliver payloads into cells by forming complexes with bioactive molecules via covalent or non-covalent bonds. Various CPPs have been applied in CPP-modified liposomes, and their effectiveness is highly regarded in liposomal drug delivery systems (DDSs). Previously, we have reported on the polyhistidine peptide (H16 peptide: HHHHHHHHHHHHHHHH-NH2 ) as a new CPP. The H16 peptide has a higher cell-penetrating capacity than well-known CPPs and delivers small molecules such as fluorescent dyes, bioactive peptides, and proteins into mammalian cells...
May 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29744842/self-assembly-of-filamentous-cell-penetrating-peptides-for-gene-delivery
#15
Dawei Xu, Louis DeRidder, Brendan Elmore, He Dong
Cell penetrating peptides (CPPs) have been proven to be an effective vector to deliver a variety of membrane-impermeable macromolecules, such as DNAs, siRNAs, and proteins. Conventional single-chain CPPs typically suffer from severe protease degradation and fast clearance rate for in vivo therapeutic delivery application. In this chapter, we show that supramolecular assembly of de novo designed cationic multidomain peptides (MDPs) leads to nanostructured filaments with increased proteolytic stability and potent membrane activity necessary for improved transfection efficiency...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29744435/fabrication-of-self-assembling-nanofibers-with-optimal-cell-uptake-and-therapeutic-delivery-efficacy
#16
Dawei Xu, Damien S K Samways, He Dong
Effective strategies to fabricate finite organic nanoparticles and understanding their structure-dependent cell interaction is highly important for the development of long circulating nanocarriers in cancer therapy. In this contribution, we will capitalize on our recent development of finite supramolecular nanofibers based on the self-assembly of modularly designed cationic multidomain peptides (MDPs) and use them as a model system to investigate structure-dependent cell penetrating activity. MDPs self-assembled into nanofibers with high density of cationic charges at the fiber-solvent interface to interact with the cell membrane...
December 2017: Bioactive Materials
https://www.readbyqxmd.com/read/29743505/contrasting-roles-for-actin-in-the-cellular-uptake-of-cell-penetrating-peptide-conjugates
#17
L He, E J Sayers, P Watson, A T Jones
The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29743422/in-vivo-imaging-technology-of-transplanted-stem-cells-using-quantum-dots-for-regenerative-medicine
#18
Hiroshi Yukawa, Yoshinobu Baba
Quantum dots (QDs) have excellent fluorescence properties in comparison to traditional fluorescence probes. Thus, the optical application of QDs is rapidly expanding to each field of analytical chemistry. In this review paper, we reviewed the application of QDs to regenerative medicine, especially stem cell transplantation therapy. The labeling of stem cells using QDs composed of semiconductor materials in combination with a chemical substance, poly-cationic liposome and cell penetrating peptide is reported...
2018: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/29740917/getting-in-emerging-methods-and-design-principles-for-cell-penetrant-peptides
#19
Leila Peraro, Joshua Kritzer
Biomolecules such as antibodies, proteins and peptides are important tools for chemical biology and leads for drug development. They have been used to inhibit a variety of extracellular proteins, but accessing intracellular proteins has been much more challenging. In this review, we discuss diverse chemical approaches that have yielded cell-penetrant peptides and identify three distinct strategies: masking backbone amides, patterning of guanidinium groups, and amphipathic patterning. We summarize a growing number of large data sets, which are starting to reveal more specific design guidelines for each strategy...
May 8, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29738229/arginine-containing-surfactant-like-peptides-interaction-with-lipid-membranes-and-antimicrobial-activity
#20
Valeria Castelletto, Ruth H Barnes, Kimon-Andreas Karatzas, Charlotte J C Edwards-Gayle, Francesca Greco, Ian W Hamley, Robert Rambo, Jani Seitsonen, Janne Ruokolainen
The activity of antimicrobial peptides stems from their interaction with bacterial membranes, which are disrupted according to a number of proposed mechanisms. Here, we investigate the interaction of a model antimicrobial peptide that contains a single arginine residue with vesicles containing model lipid membranes. The surfactant-like peptide Ala6-Arg (A6R) is studied in the form where both termini are capped (CONH-A6R-NH2, capA6R) or uncapped (NH2-A6R-OH, A6R). Lipid membranes are selected to correspond to model anionic membranes (POPE/POPG) resembling those in bacteria or model zwitterionic membranes (POPC/DOPC) similar to those found in mammalian cells...
May 8, 2018: Biomacromolecules
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