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Cell penetrating peptide

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https://www.readbyqxmd.com/read/28528116/ph-controllable-cell-penetrating-polypeptide-possessing-cancer-targeting
#1
DaeYong Lee, IlKoo Noh, Jisang Yoo, N Sanoj Rejinold, Yeu-Chun Kim
Helical peptides were naturally-occurring ordered conformations that mediated various biological functions essential for biotechnology. However, it was difficult for natural helical polypeptides to be applied in biomedical fields due to low bioavailability. To avoid these problems, synthetic alpha-helical polypeptides have recently been introduced by further modifying pendants in the side chain. In spite of an attractive biomimetic helical motif, these systems could not be tailored for targeted delivery mainly due to nonspecific binding events...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28528024/structure-diverse-phylomer-libraries-as-a-rich-source-of-bioactive-hits-from-phenotypic-and-target-directed-screens-against-intracellular-proteins
#2
REVIEW
Paul M Watt, Nadia Milech, Shane R Stone
Phylomers are peptides derived from biodiverse protein fragments. Genetically encoded Phylomer libraries have been constructed, containing hundreds of billions of peptides derived from virtually all of the few thousand fold families found in the protein universe. They offer a rich source of high quality hits against diverse target sequences and have been used for three main purposes: firstly, to identify and validate targets in phenotypic screens; secondly, to block protein interactions with nanomolar potency binding affinities; thirdly as a source of more efficient cell penetrating peptides for the delivery of a wide range of biologics...
May 18, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28525708/affinity-based-assembly-of-peptides-on-plasmonic-nanoparticles-delivered-intracellularly-with-light-activated-control
#3
Demosthenes P Morales, William Wonderly, Xiao Huang, Meghan McAdams, Amanda Chron, Norbert O Reich
We report a universal strategy for functionalizing near-infrared light-responsive nanocarriers with both a peptide "cargo" and an orthogonal cell-penetrating peptide. Modularity of both the cargo and internalization peptide attachment are an important feature of these materials relying on the robust affinity of polyhistidine tags to nitrilotriacetic acid in the presence of nickel as well as the affinity of biotin labeled peptides to streptavidin. Attachment to the gold surface uses thiol labeled scaffolds terminated with the affinity partner...
May 19, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28524768/anti-microrna-targeting-using-peptide-based-nanocomplexes-to-inhibit-differentiation-of-human-pancreatic-stellate-cells
#4
Jonas Schnittert, Praneeth R Kuninty, Tomasz F Bystry, Roland Brock, Gert Storm, Jai Prakash
AIM: To develop novel peptide-based nanocomplexes (NCs) for delivery of anti-miRNA oligonucleotides to human-derived pancreatic stellate cells (hPSCs), precursors of cancer-associated fibroblasts. MATERIALS & METHODS: NCs of anti-miRNA oligonucleotides and cell-penetrating peptides (different variants) were formed and characterized. The effects of anti-miR-199a delivery on hPSC differentiation and 3D heterospheroid formation were investigated. RESULTS: Dimeric cell-penetrating peptide based NCs (NC-2) showed 130-fold higher uptake by hPSCs compared with monomer-based NCs (NC-1) and tenfold higher uptake compared with general fibroblasts and different pancreatic tumor cells...
May 19, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28523591/assessment-of-the-neuroprotective-effects-of-arginine-rich-protamine-peptides-poly-arginine-peptides-r12-cyclic-r22-and-arginine-tryptophan-containing-peptides-following-in-vitro-excitotoxicity-and-or-permanent-middle-cerebral-artery-occlusion-in-rats
#5
Bruno P Meloni, Diego Milani, Jane L Cross, Vince W Clark, Adam B Edwards, Ryan S Anderton, David J Blacker, Neville W Knuckey
We have demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties with arginine content and peptide positive charge being particularly critical for neuroprotective efficacy. In addition, the presence of other amino acids within arginine-rich peptides, as well as chemical modifications, peptide length and cell-penetrating properties also influence the level of neuroprotection. Against this background, we have examined the neuroprotective efficacy of arginine-rich protamine peptides, a cyclic (R12-c) poly-arginine peptide and a R22 poly-arginine peptide, as well as arginine peptides containing tryptophan or other amino acids (phenylalanine, tyrosine, glycine or leucine) in in vitro glutamic acid excitotoxicity and in vivo rat permanent middle cerebral artery occlusion models of stroke...
May 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28522994/new-potent-membrane-targeting-antibacterial-peptides-from-viral-capsid-proteins
#6
Susana A Dias, João M Freire, Clara Pérez-Peinado, Marco M Domingues, Diana Gaspar, Nuno Vale, Paula Gomes, David Andreu, Sónia T Henriques, Miguel A R B Castanho, Ana S Veiga
The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28522193/ph-triggered-re-assembly-of-nanosphere-to-nanofiber-the-role-of-peptide-conformational-change-for-enhanced-cancer-therapy
#7
Peiqing Liang, Junjiong Zheng, Shulin Dai, Jiayu Wang, Zhaoqing Zhang, Ting Kang, Changyun Quan
pH-triggered conformational change and subsequent re-assembly of nanostructures provide a new strategy in nanomedicine for controlled drug release and enhanced therapy. Here, we reported the development of a novel pH-responsive nano-assembly as a drug carrier from peptide amphiphile (PA) consisting of mimicking peptide and stearic acid moieties. The mimicking peptide is a basic 17-amino acid peptide derived from antennapedia homeodomain, and undergoes a conformational transition of the secondary structure from β-sheet at pH7...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28521201/validation-of-the-use-of-an-artificial-mitochondrial-reporter-dna-vector-containing-a-cytomegalovirus-promoter-for-mitochondrial-transgene-expression
#8
Yuma Yamada, Takuya Ishikawa, Hideyoshi Harashima
Mitochondria have their own gene expression system that is independent of the nuclear system, and control cellular functions in cooperation with the nucleus. While a number of useful technologies for achieving nuclear transgene expression have been reported, only a few have focused on mitochondria. In this study, we validated the utility of an artificial mitochondrial DNA vector with a virus promoter on mitochondrial transgene expression. We designed and constructed pCMV-mtLuc (CGG) that contains a CMV promotor derived from Cytomegalovirus and an artificial mitochondrial genome with a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system...
May 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28517007/generation-of-a-cell-permeable-cycloheptapeptidyl-inhibitor-against-the-peptidyl-prolyl-isomerase-pin1
#9
Walaa Bedewy, Hui Liao, Nageh A Abou-Taleb, Sherif F Hammad, Tamer Nasr, Dehua Pei
Cyclic peptides are capable of binding and modulating challenging drug targets including protein-protein interactions. However, their lack of membrane permeability prevents their application against intracellular targets. In this study, we show that it is possible to design a cell-permeable and biologically active cycloheptapeptide inhibitor against the intracellular enzyme peptidyl-prolyl isomerase Pin1 by integrating cell-penetrating and target-binding sequences.
May 18, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28512335/arginine-rich-cell-penetrating-peptide-modified-extracellular-vesicles-for-active-macropinocytosis-induction-and-efficient-intracellular-delivery
#10
Ikuhiko Nakase, Kosuke Noguchi, Ayako Aoki, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki
Extracellular vesicles (EVs) including exosomes have been shown to play crucial roles in cell-to-cell communication because of their ability to carry biofunctional molecules (e.g., microRNAs and enzymes). EVs also have pharmaceutical advantages and are highly anticipated to be a next-generation intracellular delivery tool. Here, we demonstrate an experimental technique that uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active macropinocytosis for effective cellular EV uptake. Modification of arginine-rich CPPs on the EV membrane resulted in the activation of the macropinocytosis pathway, and the number of arginine residues in the peptide sequences affected the cellular EV uptake efficiency...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505457/molecular-and-biocompatibility-characterization-of-red-blood-cell-membrane-targeted-and-cell-penetrating-peptide-modified-polymeric-nanoparticles
#11
Kaustuv Sahoo, Sriharsha Karumuri, Rangika S Hikkaduwa Koralege, Nicholas H Flynn, Steve Hartson, Jing Liu, Joshua D Ramsey, Kaan Kalkan, Carey Pope, Ashish Ranjan
Red blood cells (RBCs) express a variety of immunomodulatory markers that enable the body to recognize them as self. We have shown that RBC membrane glycophorin A (GPA) receptor can mediate membrane attachment of protein therapeutics. A critical knowledge gap is whether attaching drug encapsulated nanoparticles (NPs) to GPA, and modification with cell penetration peptide (CPP) will impact binding, oxygenation and induce cellular stress. The objective of this study was to formulate copolymer-based NPs containing model fluorescent tagged bovine serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs), single chain variable antibody (scFv TER-119, SNPs), and low molecular weight protamine based CPP (LNPs) and determine their biocompatibility using a variety of complementary high-throughput in vitro assays...
May 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28503153/investigating-engineered-ribonucleoprotein-particles-to-improve-oral-rnai-delivery-in-crop-insect-pests
#12
François-Xavier Gillet, Rayssa A Garcia, Leonardo L P Macedo, Erika V S Albuquerque, Maria C M Silva, Maria F Grossi-de-Sa
Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being investigated largely as an RNA interference (RNAi)-based resistance strategy against crop insect pests. However, limitations of this strategy include the sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane penetration. Working with the insect pest cotton boll weevil (Anthonomus grandis), we showed that the chimeric protein PTD-DRBD (peptide transduction domain-dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein particle (RNP) that improves the effectiveness of the RNAi mechanism in the insect...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28502470/antitumoral-cascade-targeting-ligand-for-il-6-receptor-mediated-gene-delivery-to-glioma
#13
Shanshan Wang, Sören Reinhard, Chengyi Li, Min Qian, Huiling Jiang, Yilin Du, Ulrich Lächelt, Weiyue Lu, Ernst Wagner, Rongqin Huang
The effective treatment of glioma is largely hindered by the poor transfer of drug delivery systems across the blood-brain barrier (BBB) and the difficulty in distinguishing healthy and tumorous cells. In this work, for the first time, an interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide provides multiple functions, including the cascade-targeting potential represented by a combined BBB-crossing and subsequent glioma-targeting ability, as well as a direct tumor-inhibiting effect...
May 10, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28497694/stapled-rgd-peptide-enables-glioma-targeted-drug-delivery-by-overcoming-multiple-barriers
#14
Huitong Ruan, Xishan Chen, Cao Xie, Beibei Li, Man Ying, Yu Liu, Mingfei Zhang, Xuesai Zhang, Changyou Zhan, Wuyuan Lu, Weiyue Lu
Malignant glioma, the most frequent and aggressive central nervous system (CNS) tumor, severely threatens human health. One reason for its poor prognosis and short survival is the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which restrict the penetration of therapeutics into the brain at different stages of glioma. Herein, inspired by the peptide stapling technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB penetration and targeting ability to glioma cells...
May 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28496323/a-novel-nanoemulsion-based-method-to-produce-ultrasmall-water-dispersible-nanoparticles-from-chitosan-surface-modified-with-cell-penetrating-peptide-for-oral-delivery-of-proteins-and-peptides
#15
Ghullam Reza Barbari, Farid Abedin Dorkoosh, Mohsen Amini, Mohammad Sharifzadeh, Fateme Atyabi, Saeed Balalaie, Niyousha Rafiee Tehrani, Morteza Rafiee Tehrani
A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as "nano-containers and nano-reactors". The entrapped polymer chains of CS inside these "nano-reactors" are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28495577/delivery-of-anti-inflammatory-peptides-from-hollow-pegylated-poly-nipam-nanoparticles-reduces-inflammation-in-an-ex-vivo-osteoarthritis-model
#16
James McMasters, Scott Poh, Jenny B Lin, Alyssa Panitch
Targeted delivery of anti-inflammatory osteoarthritis treatments have the potential to significantly decrease undesirable systemic side effects and reduce required therapeutic dosage. Here we present a targeted, non-invasive drug delivery system to decrease inflammation in an osteoarthritis model. Hollow thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been synthesized via degradation of a N,N'-bis(acryloyl)cystamine (BAC) cross-linked core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive loading of an anti-inflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK)...
May 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28495087/gemcitabine-anti-proliferative-activity-significantly-enhanced-upon-conjugation-with-cell-penetrating-peptides
#17
Nuno Vale, Abigail Ferreira, Iva Fernandes, Cláudia Alves, Maria João Araújo, Nuno Mateus, Paula Gomes
Gemcitabine proven efficiency against a wide range of solid tumors and undergoes deamination to its inactive uridine metabolite, which underlies its low bioavailability, and tumour resistance was also associated with nucleoside transporter alterations. Hence, we have conjugated gemcitabine to cell-penetrating peptides (CPP), in an effort to both mask its aniline moiety and facilitate its delivery into cancer cells. Two CPP-drug conjugates have been synthesized and studied regarding both the time-dependent kinetics of gemcitabine release and their anti-proliferative activity on three different human cancer cell lines...
April 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28494491/topical-delivery-of-anti-vegf-drugs-to-the-ocular-posterior-segment-using-cell-penetrating-peptides
#18
Felicity de Cogan, Lisa J Hill, Aisling Lynch, Peter J Morgan-Warren, Judith Lechner, Matthew R Berwick, Anna F A Peacock, Mei Chen, Robert A H Scott, Heping Xu, Ann Logan
Purpose: To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. Methods: CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28490747/structural-basis-for-importin-%C3%AE-binding-of-the-human-immunodeficiency-virus-tat
#19
K M Smith, Z Himiari, S Tsimbalyuk, J K Forwood
HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning (48)GRKKRR, and a cell penetrating peptide (CPP) signal spanning (48)GRKKRRQRRRAPQN...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489341/smart-asymmetric-vesicles-with-triggered-availability-of-inner-cell-penetrating-shells-for-specific-intracellular-drug-delivery
#20
Junjie Li, Shiyan Xiao, Yixuan Xu, Shuai Zuo, Zengshi Zha, Wendong Ke, Chuanxin He, Zhishen Ge
Smart nanocarriers attract considerable interest in the filed of precision nanomedicine. Dynamic control of the interaction between nanocarriers and cells offers the feasibility that in situ activates cellular internalization at the targeting sites. Herein, we demonstrate a novel class of enzyme-responsive asymmetric polymeric vesicles self-assembled from matrix metalloproteinase (MMP)-cleavable peptide-linked triblock copolymer, poly(ethylene glycol)-GPLGVRG-b-poly(ε-caprolactone)-b-poly(3-guanidinopropyl methacrylamide) (PEG-GPLGVRG-PCL-PGPMA), in which the cell-penetrating PGPMA segments asymmetrically distribute in the outer and inner shells with the fractions of 9% and 91%, respectively...
May 10, 2017: ACS Applied Materials & Interfaces
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