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Cell-penetrating peptides

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https://www.readbyqxmd.com/read/29656216/insights-into-cell-penetrating-peptide-conjugated-gold-nanoparticles-for-internalization-into-bacterial-cells
#1
Munish Kumar, Werner Tegge, Nishima Wangoo, Rahul Jain, Rohit K Sharma
Gold nanoparticles (AuNPs) functionalized with different biomolecules find extensive application in therapy, clinical diagnosis and biomedical imaging. Herein, two derivatives of TAT peptide with sequences YGRKKRRQRRR and YGRKKRRQRRR-(β-ala)3 -Cys-amide were conjugated with tannic acid capped gold nanoparticles which acted as a carrier for cell penetrating peptides (CPPs) into the bacterial cells. The interaction of YGRKKRRQRRR peptide with AuNPs was non-covalent in nature whereas YGRKKRRQRRR-(β-ala)3 -Cys-amide interacted covalently with the AuNPs due to presence of thiol group in cysteine which bind strongly to gold nanoparticles surface...
March 31, 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29653223/acid-sensitive-hybrid-polymeric-micelles-containing-a-reversibly-activatable-cell-penetrating-peptide-for-tumor-specific-cytoplasm-targeting
#2
Baoqiang Tang, Jennica L Zaro, Yan Shen, Qian Chen, Yinglan Yu, Pingping Sun, Yanqi Wang, Wei-Chiang Shen, Jiasheng Tu, Chunmeng Sun
Cell-penetrating peptides (CPPs) have become a novel drug delivery system due to their distinct advantages, including high cell transmembrane potency and ability to carry cargo molecules inside cells. However, owing to their cationic charge and non-specificity characteristics, the clinical application of CPPs is limited. In the current study, we engineered a reversibly activatable cell-penetrating peptide (RACPP), containing oligoarginine fused to a pH-sensitive masking sequence via a polyglycine linker ((HE)10 G5 R6 or HE-CPP) with ultra-pH-sensitivity...
April 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29651964/poly-l-arginine-enhancing-cytotoxicity-and-cellular-uptake-of-doxorubicin-and-necrotic-cell-death
#3
Bahareh Movafegh, Razieh Jalal, Zobeideh Mohammadi
OBJECTIVE: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. METHODS: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay...
April 11, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29648441/biocompatible-polymers-modified-with-d-octaarginine-as-an-absorption-enhancer-for-nasal-peptide-delivery
#4
Kohei Miyata, Masami Ukawa, Kohta Mohri, Kozue Fujii, Mako Yamada, Sohei Tanishita, Satoshi Higashitarumi, Seiya Ishizaki, Hironori Kumagai, Kyohei Ochiai, Ken-Ichiro Hiwatari, Kazufumi Tsubaki, Koichi Shigeno, Etsuo Tobita, Hideo Kobayashi, Shinji Sakuma
Peptide and protein drugs, which are categorized as biologics, exhibit poor membrane permeability. This pharmacokinetic disadvantage has largely restricted the development of non-invasive dosage forms of biologics that deliver into systemic circulation. We have been investigating the potential use of cell-penetrating peptide-linked polymers as a novel absorption enhancer to overcome this challenge. Since our previous study revealed that biocompatible poly(N-vinylacetamide-co-acrylic acid) modified with D-octaarginine, a typical cell-penetrating peptide, enhanced in vitro permeation of biomolecules such as plasmid DNA and bovine serum albumin through cell membranes, the present study evaluated if the polymers enhanced in vivo absorption of biologics applied on the mucosa...
April 12, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29643997/new-antimicrobial-peptide-kills-drug-resistant-pathogens-without-detectable-resistance
#5
Jong-Kook Lee, Tudor Luchian, Yoonkyung Park
Clavaspirin peptide (CSP) is derived from the pharyngeal tissues of the tunicate Styela clava . The 23-amino acid peptide is histidine-rich and amidated at the N-terminus. CSP possesses low antimicrobial and high hemolytic activity at pH 7.4. Therefore, we designed 4 CSP analogs with substituted hydrophobic amino acids to reduce hydrophobic amino acid interactions. These modifications reduced the aggregation and cytotoxicity of the analogs at pH 7.4. The analogs also showed potent antimicrobial activity by accumulating on bacterial cell surfaces and inducing the lytic mechanism against gram-negative and gram-positive cells at pH 5...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643807/antimicrobial-peptides-and-their-therapeutic-potential-for-bacterial-skin-infections-and-wounds
#6
REVIEW
Anja Pfalzgraff, Klaus Brandenburg, Günther Weindl
Alarming data about increasing resistance to conventional antibiotics are reported, while at the same time the development of new antibiotics is stagnating. Skin and soft tissue infections (SSTIs) are mainly caused by the so called ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species) which belong to the most recalcitrant bacteria and are resistant to almost all common antibiotics. S. aureus and P. aeruginosa are the most frequent pathogens isolated from chronic wounds and increasing resistance to topical antibiotics has become a major issue...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29625989/a-cell-penetrating-peptide-fused-phage-lysin-kills-intracellular-mrsa-in-keratinocytes-and-treatment-for-skin-infections-of-mice
#7
ZhaoFei Wang, LiCheng Kong, Yang Liu, Qiang Fu, ZeLin Cui, Jian Wang, JingJiao Ma, HengAn Wang, YaXian Yan, JianHe Sun
Staphylococcus aureus ( S. aureus ) is the major pathogen that causes skin and skin structure infections, which is able to survive and persist in keratinocytes of the epidermis. Since the evolution of multi-drug resistant bacteria, the use of phages and their lysins presents a promising alternative approach. In this study, a cell wall hydrolase (also called lysin) derived from Staphylococcus phage JD007, short for JDlys, was identified. The JDlys showed a strong lytic activity against MRSA strains from different sources and multilocus sequence typing (MLST) types...
April 6, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29621495/vesicles-mimicking-normal-and-cancer-cell-membranes-exhibit-differential-responses-to-the-cell-penetrating-peptide-pep-1
#8
Bashiyar Almarwani, Esther Nzuzi Phambu, Christopher Alexander, Ha Aimee T Nguyen, Nsoki Phambu, Anderson Sunda-Meya
The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques...
April 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29619854/tf-ligand-receptor-mediated-exenatide-zn-2-complex-oral-delivery-system-for-penetration-enhancement-of-exenatide
#9
Liping Zhang, Yanan Shi, Yina Song, Dongyu Duan, Xuemei Zhang, Kaoxiang Sun, Youxin Li
Safe and effective oral delivery of peptide is a challenge. Here, we used exenatide and zinc ions (Zn2+ ) to form a complex to explore a meaningful oral-targeted drug-delivery system. Polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA) was used to prepare nanoparticles (NPs) to escape the degradation caused by gastrointestinal enzymes. Transferrin (Tf) was used as a targeting group. PEG-PLGA-NPs and Tf-modified exenatide-Zn2+ -loaded NPs (Tf-PEG-PLGA-NPs) were uniformly sized spheres according to transmission electron microscopy...
April 5, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29619166/peptide-cas9-nanostructures-for-ribonucleoprotein-cell-membrane-transport-and-gene-edition
#10
Irene Lostalé-Seijo, Iria Louzao, Marisa Juanes, Javier Montenegro
The discovery of RNA guided endonucleases has emerged as one of the most important tools for gene edition and biotechnology. The selectivity and simplicity of the CRISPR/Cas9 strategy allows the straightforward targeting and editing of particular loci in the cell genome without the requirement of protein engineering. However, the transfection of plasmids encoding the Cas9 and the guide RNA could lead to undesired permanent recombination and immunogenic responses. Therefore, the direct delivery of transient Cas9 ribonucleoprotein constitutes an advantageous strategy for gene edition and other potential therapeutic applications of the CRISPR/Cas9 system...
December 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29617431/membrane-permeabilizing-amphiphilic-peptide-delivers-recombinant-transcription-factor-and-crispr-cas9-cpf1-ribonucleoproteins-in-hard-to-modify-cells
#11
Thomas Del'Guidice, Jean-Pascal Lepetit-Stoffaes, Louis-Jean Bordeleau, Joannie Roberge, Vanessa Théberge, Coraline Lauvaux, Xavier Barbeau, Jessica Trottier, Vibhuti Dave, Denis-Claude Roy, Bruno Gaillet, Alain Garnier, David Guay
Delivery of recombinant proteins to therapeutic cells is limited by a lack of efficient methods. This hinders the use of transcription factors or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) ribonucleoproteins to develop cell therapies. Here, we report a soluble peptide designed for the direct delivery of proteins to mammalian cells including human stem cells, hard-to-modify primary natural killer (NK) cells, and cancer cell models. This peptide is composed of a 6x histidine-rich domain fused to the endosomolytic peptide CM18 and the cell penetrating peptide PTD4...
2018: PloS One
https://www.readbyqxmd.com/read/29615400/neth2pan-a-computational-tool-to-guide-mhc-peptide-prediction-on-murine-tumors
#12
Christa I DeVette, Massimo Andreatta, Wilfried Bardet, Steven J Cate, Vanessa I Jurtz, Kenneth W Jackson, Alana L Welm, Morten Nielsen, William H Hildebrand
With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB genetic background, and one such model is the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse - an immunocompetent transgenic mouse that exhibits spontaneous mammary tumor development and metastasis with high penetrance...
April 3, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29614254/mechanistic-studies-of-a-cell-permeant-peptide-designed-to-enhance-myosin-light-chain-phosphorylation-in-polarized-intestinal-epithelia
#13
Khaled Almansour, Alistair Taverner, Ian M Eggleston, Randall J Mrsny
Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS19 ) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH2 ) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character...
March 31, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29607986/-development-of-noninvasive-drug-delivery-systems-to-the-brain-for-the-treatment-of-brain-central-nervous-system-diseases
#14
Takanori Kanazawa
 In general, the blood-brain barrier (BBB) poses a major challenge to drug development efforts targeting brain/central nervous system (CNS) diseases, since it limits the distribution of systemically administered therapeutics to the brain/ CNS. Therefore, the development of effective strategies for enhancing drug delivery to the brain has been a topic of great interest in both the clinical and pharmaceutical fields. Intranasal administration has been noted as a method for noninvasive delivery of a drug to the brain/CNS by bypassing the BBB via the "nose-to-brain" route...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29607927/noncovalent-strategy-with-cell-penetrating-peptides-to-facilitate-the-brain-delivery-of-insulin-through-the-blood-brain-barrier
#15
Noriyasu Kamei, Ai Yamaoka, Yukiko Fukuyama, Rei Itokazu, Mariko Takeda-Morishita
To overcome the difficulty in delivery of biopharmaceuticals such as peptides and proteins to the brain, several approaches combining the ligands and antibodies targeting the blood-brain barrier (BBB) have been tried. However, these are inefficient in terms of their permeability through the BBB and structural modification of bioactive drugs. In the present study, we therefore examined the usefulness of a noncovalent method using the cell-penetrating peptides (CPPs) such as octaarginine (R8) as a suitable brain delivery strategy for biopharmaceuticals...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29603441/cell-penetrating-peptides-containing-fluorescent-d-cysteines
#16
Claudio D Navo, Alicia Asín, Eva Gómez-Orte, Marta I Gutiérrez-Jiménez, Ismael Compañón, Begoña Ezcurra, Alberto Avenoza, Jesús H Busto, Francisco Corzana, María M Zurbano, Gonzalo Jiménez-Osés, Juan Cabello, Jesús Peregrina
A series of fluorescent D-cysteines (Cys) has been synthesized and their optical properties were studied. The key synthetic step is the highly diastereoselective 1,4-conjugate addition of aryl thiols to a chiral bicyclic dehydroalanine recently developed by our group. This reaction is fast at room temperature and proceeds with total chemo- and stereoselectivity. The Michael adducts were easily transformed into the corresponding amino acids to study their optical properties and, in some selected cases, into the corresponding N-Fmoc-D-cysteine derivatives to be used in solid phase peptide synthesis (SPPS)...
March 30, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29601540/cell-penetrating-capacity-and-internalization-mechanisms-used-by-the-synthetic-peptide-cigb-552-and-its-relationship-with-tumor-cell-line-sensitivity
#17
Soledad Astrada, Julio Raúl Fernández Massó, Maribel G Vallespí, Mariela Bollati-Fogolín
CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced...
March 30, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29596873/highly-efficacious-and-specific-anti-glioma-chemotherapy-by-tandem-nanomicelles-co-functionalized-with-brain-tumor-targeting-and-cell-penetrating-peptides
#18
Yaqin Zhu, Yu Jiang, Fenghua Meng, Chao Deng, Ru Cheng, Jian Zhang, Jan Feijen, Zhiyuan Zhong
Glioma is a highly challenging human malignancy as drugs typically exhibit a low blood-brain barrier (BBB) permeability as well as poor glioma selectivity and penetration. Here, we report that tandem nanomicelles co-functionalized with brain tumor-targeting and cell-penetrating peptides, Angiopep-2 and TAT, enable a highly efficacious and specific anti-glioma chemotherapy. Interestingly, tandem nanomicelles with 20 mol% Angiopep-2 and 10 mol% TAT linked via long and short poly(ethylene glycol)s, respectively, while maintaining a high glioma cell selectivity display markedly enhanced BBB permeation, glioma accumulation and penetration, and glioma cell uptake...
March 26, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29588159/a-brain-targeting-functionalized-liposomes-of-the-dopamine-derivative-n-3-4-bis-pivaloyloxy-dopamine-for-treatment-of-parkinson-s-disease
#19
Mengke Qu, Qing Lin, Shanshan He, Luyao Wang, Yao Fu, Zhirong Zhang, Ling Zhang
Parkinson's disease (PD) remains one of the most common neurodegenerative movement disorders with limited treatment options available. A dopamine derivative N-3,4-bis(pivaloyloxy)-dopamine (BPD) previously developed in our group has demonstrated superior therapeutic outcome compared to levodopa in a PD mice model. To further improve the therapeutic performance of BPD, a brain targeted drug delivery system was designed using a 29 amino-acid peptide (RVG29) derived from rabies virus glycoprotein as the targeting ligand...
March 26, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29582996/conventional-flow-liquid-chromatography-mass-spectrometry-for-exploratory-bottom-up-proteomic-analyses
#20
Juraj Lenco, Marie Vajrychova, Kristyna Pimkova, Magdaléna Prokšová, Marketa Benkova, Jana Klimentová, Vojtech Tambor, Ondrej Soukup
Due to its sensitivity and productivity, bottom-up proteomics based on liquid chromatography-mass spectrometry (LC-MS) has become the core approach in the field. The de facto standard LC-MS platform for proteomics operates at sub-µL/min flow rates, and nanospray is required for efficiently introducing peptides into a mass spectrometer. Although this is almost a "dogma", this view is being reconsidered in light of developments in highly efficient chromatographic columns, and especial-ly with the introduction of exceptionally sensitive MS instruments...
March 27, 2018: Analytical Chemistry
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