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Cell penetrating peptides

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https://www.readbyqxmd.com/read/28647433/targeted-release-of-transcription-factors-for-human-cell-reprogramming-by-zebra-cell-penetrating-peptide
#1
Benjamin Caulier, Lionel Berthoin, Helène Coradin, Frédéric Garban, Marie Claire Dagher, Benoît Polack, Bertrand Toussaint, Jean Luc Lenormand, David Laurin
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements...
June 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28647135/ultrasound-dependent-cytoplasmic-internalization-of-a-peptide-sonosensitizer-conjugate
#2
Yuki Inaba, Kazunori Watanabe, Mizuki Kitamatsu, Eiji Nakata, Atsushi Harada, Takashi Ohtsuki
A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells...
June 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28644728/liposomes-equipped-with-cell-penetrating-peptide-br2-enhances-chemotherapeutic-effects-of-cantharidin-against-hepatocellular-carcinoma
#3
Xue Zhang, Congcong Lin, Aiping Lu, Ge Lin, Huoji Chen, Qiang Liu, Zhijun Yang, Hongqi Zhang
A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28644007/cyclotides-as-tools-in-chemical-biology
#4
Simon J de Veer, Joachim Weidmann, David J Craik
Among the various molecules that plants produce for defense against pests and pathogens, cyclotides stand out as exceptionally stable and structurally unique. These ribosomally synthesized peptides are around 30 amino acids in size, and are stabilized by a head-to-tail cyclic peptide backbone and three disulfide bonds that form a cystine knot. They occur in certain plants of the Rubiaceae, Violaceae, Cucurbitaceae, Fabaceae, and Solanaceae families, with an individual plant producing up to hundreds of different cyclotides...
June 23, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28643952/asn194lys-mutation-in-rvg29-peptide-increases-gfp-transgene-delivery-by-endocytosis-to-neuroblastoma-and-astrocyte-cells
#5
Sheila Adela Villa-Cedillo, Humberto Rodríguez-Rocha, Laura Mireya Zavala-Flores, Roberto Montes-de-Oca-Luna, Aracely García-García, Maria de Jesus Loera-Arias, Odila Saucedo-Cárdenas
OBJECTIVES: A cell-penetrating peptide-based delivery system could target specific types of cells for therapeutic genes delivery. To increase the gene delivery efficiency into neuronal phenotype cells, we introduced an Asn194Lys mutation to RVG29 peptide derived from rabies virus glycoprotein and added a nuclear localization signal to enhance its nuclear import. METHODS: Mutant RVG or wild-type RVG peptide, a karyophilic peptide (KP) and a plasmid encoding green fluorescent protein (pGL) were bound by electrostatic charges to form four different kinds of RVG complexes...
June 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28643330/muc1-c-is-a-target-in-lenalidomide-resistant-multiple-myeloma
#6
Li Yin, Ashujit Tagde, Reddy Gali, Yu-Tzu Tai, Teru Hideshima, Kenneth Anderson, David Avigan, Donald Kufe
Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly expressed by MM cells and protects against reactive oxygen species (ROS)-mediated MM cell death. The present studies demonstrate that targeting MUC1-C with GO-203, a cell-penetrating peptide inhibitor of MUC1-C homodimerization, is more than additive with LEN in downregulating the WNT/β-catenin pathway, suppressing MYC, and inducing late apoptosis/necrosis...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28639251/regulation-of-the-extracellular-serpina5-protein-c-inhibitor-penetration-through-cellular-membranes
#7
Felix C Wahlmüller, Hanjiang Yang, Margareta Furtmüller, Margarethe Geiger
It is generally accepted that the phospholipid bilayer of the cell membrane is impermeable for proteins and peptides and that these molecules require special mechanisms for their transport from the extra- to the intracellular space. Recently there is increasing evidence that certain proteins/peptides can also directly cross the phospholipid membrane. SERPINA5 (protein C inhibitor) is a secreted protease inhibitor with broad protease reactivity and wide tissue distribution. It binds glycosaminoglycans and certain phospoholipids, which can modulate its inhibitory activity...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28638470/bright-polymer-dots-tracking-stem-cell-engraftment-and-migration-to-injured-mouse-liver
#8
Dandan Chen, Qiong Li, Zihui Meng, Lei Guo, Ying Tang, Zhihe Liu, Shengyan Yin, Weiping Qin, Zhen Yuan, Xuanjun Zhang, Changfeng Wu
Stem cell therapy holds promise for treatment of intractable diseases and injured organs. For clinical translation, it is pivotal to understand the homing, engraftment, and differentiation processes of stem cells in a living body. Here we report near-infrared (NIR) fluorescent semiconductor polymer dots (Pdots) for bright labeling and tracking of human mesenchymal stem cells (MSCs). The Pdots exhibit narrow-band emission at 775 nm with a quantum yield of 22%, among the highest value for various NIR probes. The Pdots together with a cell penetrating peptide are able to track stem cells over two weeks without disturbing their multipotent properties, as confirmed by the analyses on cell proliferation, differentiation, stem-cell markers, and immunophenotyping...
2017: Theranostics
https://www.readbyqxmd.com/read/28636389/tumor-microenvironment-responsive-multistaged-nanoplatform-for-systemic-rnai-and-cancer-therapy
#9
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Mikyung Yu, Morteza Mahmoudi, Jonathan Rasmussen, Dana Ayyash, Yuxiao Zhou, Omid C Farokhzad, Jinjun Shi
While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core...
June 26, 2017: Nano Letters
https://www.readbyqxmd.com/read/28636382/development-of-efficient-chemistry-to-generate-site-specific-disulfide-linked-protein-and-peptide-payload-conjugates-application-to-thiomab%C3%A2-antibody-drug-conjugates
#10
Jack David Sadowsky, Thomas H Pillow, Jinhua Chen, Fang Fan, Changrong He, Yanli Wang, Gang Yan, Hui Yao, Zijin Xu, Shanique Martin, Donglu Zhang, Phillip Chu, Josefa Dela Cruz-Chuh, Aimee O'Donohue, Guangmin Li, Geoffrey Del Rosario, Jintang He, Luna Liu, Carl K Ng, Dian Su, Gail D Lewis Phillips, Katherine Ruth Kozak, Shang-Fan Yu, Keyang Xu, Douglas Leipold, John S Wai
Conjugation of small molecule payloads to specific cysteine residues on proteins via a disulfide bond represents an attractive strategy to generate redox-sensitive bioconjugates, which have value as potential diagnostic reagents or therapeutics. Advancement of such "direct-disulfide" bioconjugates to the clinic necessitates chemical methods to form disulfide connections efficiently, without byproducts. The disulfide connection must also be resistant to premature cleavage by thiols prior to arrival at the targeted tissue...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28636317/downsizing-proto-oncogene-cfos-to-short-helix-constrained-peptides-that-bind-jun
#11
Daniel Baxter, Samuel R Perry, Timothy A Hill, W Mei Kok, Nathan R Zaccai, R Leo Brady, David P Fairlie, Jody M Mason
The oncogenic transcription factor activator protein-1 (AP-1) is a DNA-binding protein that assembles through dimerization of Fos and Jun protein subunits, their leucine-rich helical sequences entwining into a coiled-coil structure. This study reports on downsizing the proto-oncogene cFos protein (380 residues) to shorter peptides (37-25 residues) modified with helix-inducing constraints to enhance binding to Jun. A crystal structure is reported for a 37-residue Fos-derived peptide (FosW) bound to Jun. This guided iterative downsizing of FosW to shorter peptide sequences that were constrained into stable water-soluble α-helices by connecting amino acid side chains to form cyclic pentapeptide components...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28634358/hiv-1-gp41-targeting-fusion-inhibitory-peptides-enhance-the-gp120-targeting-protein-mediated-inactivation-of-hiv-1-virions
#12
Qianqian Qi, Qian Wang, Weizao Chen, Lanying Du, Dimiter S Dimitrov, Lu Lu, Shibo Jiang
Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT)...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28634138/intracellular-and-transdermal-protein-delivery-mediated-by-non-covalent-interactions-with-a-synthetic-guanidine-rich-molecular-carrier
#13
Jungkyun Im, Sanket Das, Dongjun Jeong, Chang-Jin Kim, Hyun-Suk Lim, Ki Hean Kim, Sung-Kee Chung
The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins...
June 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28631963/tumor-penetrating-peptide-integrated-thermally-sensitive-liposomal-doxorubicin-enhances-efficacy-of-radiofrequency-ablation-in-liver-tumors
#14
Fei Yan, Song Wang, Wei Yang, S Nahum Goldberg, Hao Wu, Wan-Lu Duan, Zhi-Ting Deng, Hai-Bo Han, Hai-Rong Zheng
Purpose To investigate the role of a tumor-penetrating peptide (internalizing CRGDRGPDC [iRGD])-integrated thermally sensitive liposomal (TSL) doxorubicin (DOX) in combination with radiofrequency (RF) ablation of liver tumors in an animal model. Materials and Methods Approval from the institutional animal care and use committee was obtained. Characterization of iRGD-TSL-DOX was performed in vitro. Next, H22 liver adenocarcinomas were implanted in 138 mice in vivo. The DOX accumulation and cell apoptosis of iRGD-TSL-DOX and TSL-DOX with or without RF were evaluated (n = 5) at different time points after treatment with quantitative analysis or pathologic staining...
June 19, 2017: Radiology
https://www.readbyqxmd.com/read/28629518/analysis-of-the-asymmetry-of-activated-epo-receptor-enables-designing-small-molecule-agonists
#15
Frank Guarnieri
Amgen solved the high-resolution cocrystal structure of erythropoietin (EPO) bound to the extracellular part of the receptor (EPOR) in 1998, which reveals that the EPO-EPOR interaction surface is formed by 11 salt bridges, 17 H-bonds, and 2 hydrophobic clusters centered at a pair of crucial phenylalanines (F93). The EPOR has two domains, one that penetrates the membrane and a second extracellular domain that forms one arm of the binding site for the EPO ligand. The complete competent receptor-binding site is a homodimer of EPOR with the two arms forming a funnel-shaped cup where EPO binds...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28626568/dual-targeted-peptide-conjugated-multifunctional-fluorescent-probe-with-aiegen-for-efficient-nucleus-specific-imaging-and-long-term-tracing-of-cancer-cells
#16
Yong Cheng, Chunli Sun, Xiaowen Ou, Bifeng Liu, Xiaoding Lou, Fan Xia
Precisely targeted transportation of a long-term tracing regent to a nucleus with low toxicity is one of the most challenging concerns in revealing cancer cell behaviors. Here, we report a dual-targeted peptide-conjugated multifunctional fluorescent probe (cNGR-CPP-NLS-RGD-PyTPE, TCNTP) with aggregation-induced emission (AIE) characteristic, for efficient nucleus-specific imaging and long-term and low-toxicity tracing of cancer cells. TCNTP mainly consists of two components: one is a functionalized combinatorial peptide (TCNT) containing two targeted peptides (cNGR and RGD), a cell-penetrating peptide (CPP) and a nuclear localization signal (NLS), which can specifically bind to a cell surface and effectively enter into the nucleus; the other one is an AIE-active tetraphenylethene derivative (PyTPE, a typical AIEgen) as fluorescence imaging reagent...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28624185/the-formation-of-nanoparticles-between-small-interfering-rna-and-amphipathic-cell-penetrating-peptides
#17
Ly Pärnaste, Piret Arukuusk, Kent Langel, Tanel Tenson, Ülo Langel
Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28620219/molecular-dynamics-exploration-of-poration-and-leaking-caused-by-kalata-b1-in-hiv-infected-cell-membrane-compared-to-host-and-hiv-membranes
#18
Wanapinun Nawae, Supa Hannongbua, Marasri Ruengjitchatchawalya
The membrane disruption activities of kalata B1 (kB1) were investigated using molecular dynamics simulations with membrane models. The models were constructed to mimic the lipid microdomain formation in membranes of HIV particle, HIV-infected cell, and host cell. The differences in the lipid ratios of these membranes caused the formation of liquid ordered (lo) domains of different sizes, which affected the binding and activity of kB1. Stronger kB1 disruptive activity was observed for the membrane with small sized lo domain...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617063/matrix-metalloproteases-responsive-nanomaterials-for-tumor-targeting-diagnosis-and-treatment
#19
Jingyuan Xiong, Huile Gao
Tumor poses tremendous challenges to mankind. In various tumors, matrix metalloproteases (MMPs) are ubiquitously over expressed and participate throughout the process of tumor development. MMPs are commonly used as internal stimuli, and MMPs responsive nanomaterials are classified into three categories according to the drug delivery process: administration and distribution to tumor, intratumoral distribution and cell internalization, and specific drug release. Firstly, MMPs sensitive polyethylene glycol (PEG) de-shielding and activatable cell penetrating peptides were developed to improve the blood circulation time of drug delivery systems, thereby, enhancing tumor or stroma cells recognition and penetration...
June 15, 2017: Journal of Microencapsulation
https://www.readbyqxmd.com/read/28614654/creation-of-a-synthetic-ligand-for-mitochondrial-dna-sequence-recognition-and-promoter-specific-transcription-suppression
#20
Takuya Hidaka, Ganesh N Pandian, Junichi Taniguchi, Tomohiro Nobeyama, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Synthetic ligands capable of recognizing the specific DNA sequences inside human mitochondria and modulating gene transcription is of increasing demand because of the surge in evidence linking mitochondrial genome and diseases. Herein, we created a new type of mitochondria-specific synthetic ligand, termed MITO-PIPs by conjugating a mitochondria-penetrating peptide with pyrrole-imidazole polyamides (PIPs). The designed MITO-PIPs showed specific localization inside mitochondria in HeLa cells and recognized the target DNA in a sequence-specific manner...
June 14, 2017: Journal of the American Chemical Society
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