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Cell penetrating peptides

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https://www.readbyqxmd.com/read/28432017/dual-functional-nanoparticles-for-precise-drug-delivery-to-alzheimer-s-disease-lesions-targeting-mechanisms-pharmacodynamics-and-safety
#1
Xiaoyao Zheng, Chi Zhang, Qian Guo, Xu Wan, Xiayan Shao, Qingfeng Liu, Qizhi Zhang
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the cerebral accumulation of extracellular amyloid plaques. In a previous study, this histopathological hallmark was used as a target on a dual-functional nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide, a β-sheet breaker, to AD lesions precisely. This delivery system could reduce the amyloid-β (Aβ) burden in the brains of AD model mice, as well as ameliorated the memory impairment of the mice...
April 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28431917/effective-modification-of-cell-death-inducing-intracellular-peptides-by-means-of-a-photo-cleavable-peptide-array-based-screening-system
#2
Ikko Kozaki, Kazunori Shimizu, Hiroyuki Honda
Intracellular functional peptides that play a significant role inside cells have been receiving a lot of attention as regulators of cellular activity. Previously, we proposed a novel screening system for intracellular functional peptides; it combined a photo-cleavable peptide array system with cell-penetrating peptides (CPPs). Various peptides can be delivered into cells and intracellular functions of the peptides can be assayed by means of our system. The aim of the present study was to demonstrate that the proposed screening system can be used for assessing the intracellular activity of peptides...
April 18, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28431354/first-example-of-peptides-targeting-the-dimer-interface-of-leishmania-infantum-trypanothione-reductase-with-potent-in%C3%A2-vitro-antileishmanial-activity
#3
Marta Ruiz-Santaquiteria, Pedro A Sánchez-Murcia, Miguel A Toro, Héctor de Lucio, Kilian Jesús Gutiérrez, Sonia de Castro, Filipa A C Carneiro, Federico Gago, Antonio Jiménez-Ruiz, María-José Camarasa, Sonsoles Velázquez
A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem2013) has been designed and synthesized by introduction of the lactam between amino acid side chains that are separated by one helical turn (i, i+4). All of these compounds were tested in vitro as both dimerization and enzyme inhibitors of Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR in the low micromolar range and they also disrupted enzyme dimerization...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430394/structure-based-design-of-a-new-scaffold-for-cell-penetrating-peptidic-inhibitors-of-the-histone-demethylase-phf8
#4
Jerzy Dorosz, Lars Olsen, Signe Teuber Seger, Cornelia Steinhauer, Giorgos Bouras, Charlotte Helgstrand, Anders Wiuf, Michael Gajhede
The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated lysine 9 on histone H3 (H3K9me1/2) and is a transcriptional activator involved in development and cancer. Affinity and specificity of PHF8 towards H3K9me2 substrate is affected by interaction with both the catalytic domain and a PHD reader domain. The latter specifically recognizes tri-methylated lysine 4 on histone H3. A fragment of the histone H3 tail with tri-methylated lysine 4 was used as template for structure based design of a cyclic, cell-penetrating peptide that exhibits micromolar binding affinity to PHF8 in biochemical assays...
April 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28428051/cell-penetrating-peptide-cgkrk-mediates-efficient-and-widespread-targeting-of-bladder-mucosa-following-focal-injury
#5
James I Griffin, Siu Kit Kevin Cheng, Tomoko Hayashi, Dennis Carson, Manju Saraswathy, Devatha P Nair, Dmitri Simberg
The bladder presents an attractive target for topical drug delivery. The barrier function of the bladder mucosa (urothelium) presents a penetration challenge for small molecules and nanoparticles. We found that focal mechanical injury of the urothelium greatly enhances the binding and penetration of intravesically-administered cell-penetrating peptide CGKRK (Cys-Gly-Lys-Arg-Lys). Notably, the CGKRK bound to the entire urothelium, and the peptide was able to penetrate into the muscular layer. This phenomenon was not dependent on intravesical bleeding and was not caused by an inflammatory response...
April 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28421460/flow-arrest-intra-arterial-delivery-of-small-tat-decorated-and-neutral-micelles-to-gliomas
#6
Juliane Nguyen, Shaolie S Hossain, Johann R N Cooke, Jason A Ellis, Michael B Deci, Charles W Emala, Jeffrey N Bruce, Irving J Bigio, Robert M Straubinger, Shailendra Joshi
The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28420679/tumor-microenvironment-targeting-and-responsive-peptide-based-nanoformulations-for-improved-tumor-therapy
#7
Hao Qin, Yanping Ding, Ayeesha Mujeeb, Ying Zhao, Guangjun Nie
Tumor microenvironment participates in all stages of tumor progression and has emerged as a promising therapeutic target for cancer therapy. Rapid progress in the field of molecular self-assembly using various biological molecules has resulted in the fabrication of nanoformulations, specifically targeting and regulating the microenvironment components to inhibit tumor malignancies. This inhibition process is based on the differentiating biophysicochemical cues guiding tumor and normal tissue microenvironments...
April 18, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28420127/glycosaminoglycan-binding-and-non-endocytic-membrane-translocation-of-cell-permeable-octaarginine-monitored-by-real-time-in-cell-nmr-spectroscopy
#8
Yuki Takechi-Haraya, Kenzo Aki, Yumi Tohyama, Yuichi Harano, Toru Kawakami, Hiroyuki Saito, Emiko Okamura
Glycosaminoglycans (GAGs), which are covalently-linked membrane proteins at the cell surface have recently been suggested to involve in not only endocytic cellular uptake but also non-endocytic direct cell membrane translocation of arginine-rich cell-penetrating peptides (CPPs). However, in-situ comprehensive observation and the quantitative analysis of the direct membrane translocation processes are challenging, and the mechanism therefore remains still unresolved. In this work, real-time in-cell NMR spectroscopy was applied to investigate the direct membrane translocation of octaarginine (R8) into living cells...
April 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#9
Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E Nel, Huan Meng
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414223/diversity-oriented-stapling-yields-intrinsically-cell-penetrant-inducers-of-autophagy
#10
Leila Peraro, Zhongju Zou, Kamlesh M Makwana, Ashleigh Cummings, Haydn L Ball, Hongtao Yu, Yu-Shan Lin, Beth Levine, Joshua A Kritzer
Autophagy is an essential pathway by which cellular and foreign material are degraded and recycled in eukaryotic cells. Induction of autophagy is a promising approach for treating diverse human diseases, including neurodegenerative disorders and infectious diseases. Here, we report the use of a diversity-oriented stapling approach to produce autophagy-inducing peptides that are intrinsically cell-penetrant. These peptides induce autophagy at micromolar concentrations in vitro, have aggregate-clearing activity in a cellular model of Huntington's disease, and induce autophagy in vivo...
April 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28412744/mitochondrial-vdac1-based-peptides-attacking-oncogenic-properties-in-glioblastoma
#11
Anna Shteinfer-Kuzmine, Tasleem Arif, Yakov Krelin, Shambhoo Sharan Tripathi, Avijit Paul, Varda Shoshan-Barmatz
Glioblastoma multiforme (GBM), a primary brain malignancy characterized by high morbidity, invasiveness, proliferation, relapse and mortality, is resistant to chemo- and radiotherapies and lacks effective treatment. GBM tumors undergo metabolic reprograming and develop anti-apoptotic defenses. We targeted GBM with a peptide derived from the mitochondrial protein voltage-dependent anion channel 1 (VDAC1), a key component of cell energy, metabolism and apoptosis regulation. VDAC1-based cell-penetrating peptides perturbed cell energy and metabolic homeostasis and induced apoptosis in several GBM and GBM-derived stem cell lines...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412555/one-dimensional-poly-l-lysine-block-poly-l-threonine-assemblies-exhibit-potent-anticancer-activity-by-enhancing-membranolysis
#12
Yu-Fon Chen, Ai-Li Shiau, Sue-Joan Chang, Nai-Shin Fan, Chung-Teng Wang, Chao-Liang Wu, Jeng-Shiung Jan
Herein, we report the oncolytic activity of cationic, one-dimensional (1D) fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via the mitochondria-lytic effect. The concept is analogous to that of 1D drug carriers that exhibit enhanced cell penetration...
April 12, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28412450/pegylated-doxorubicin-nanoparticles-mediated-by-hn-1-peptide-for-targeted-treatment-of-oral-squamous-cell-carcinoma
#13
Yue Wang, Guoyun Wan, Zhiyuan Li, Shurui Shi, Bowei Chen, Chunyu Li, Lianyun Zhang, Yinsong Wang
HN-1, a 12-amino acid peptide, has been reported to possess strong capabilities for targeting and penetrating head and neck squamous cell carcinoma. Here, we designed a simple but effective nanoparticle system for the delivery of doxorubicin (DOX) targeting oral squamous cell carcinoma (OSCC) through the mediation of HN-1. PEGylated DOX (PD) was firstly synthesized by the conjugation of DOX with bis-amino-terminated poly(ethylene glycol) via succinyl linkage, and then PD nanoparticles were prepared by a modified nanoprecipitation method...
April 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28411183/membrane-permeation-of-arginine-rich-cell-penetrating-peptides-independent-of-transmembrane-potential-as-a-function-of-lipid-composition-and-membrane-fluidity
#14
Rike Wallbrecher, Tobias Ackels, R Alis Olea, Marco J Klein, Lucie Caillon, Jürgen Schiller, Petra H Bovée-Geurts, Toin H van Kuppevelt, Anne S Ulrich, Marc Spehr, Merel J W Adjobo-Hermans, Roland Brock
Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential...
April 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28405164/a-dual-mediated-liposomal-drug-delivery-system-targeting-the-brain-rational-construction-integrity-evaluation-across-the-blood-brain-barrier-and-the-transporting-mechanism-to-glioma-cells
#15
Chang Liu, Xiao-Na Liu, Gui-Ling Wang, Yu Hei, Shuai Meng, Ling-Fei Yang, Lan Yuan, Ying Xie
As the global population ages, cancer rates increase worldwide, and degenerative diseases of the central nervous system (CNS), brain tumors, and inflammation threaten human health more frequently. We designed a dual-mediated (receptor-mediated and adsorption-mediated) liposome, named transferrin-cell penetrating peptide-sterically stabilized liposome (TF-CPP-SSL), to improve therapy for gliomas through combining molecular recognition of transferrin receptors (TF-Rs) on the blood-brain barrier (BBB) and glioma cells with the internalization and lysosomal escaping ability of CPP...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28405163/enhancing-sirna-based-cancer-therapy-using-a-new-ph-responsive-activatable-cell-penetrating-peptide-modified-liposomal-system
#16
Bai Xiang, Xue-Li Jia, Jin-Long Qi, Li-Ping Yang, Wei-Hong Sun, Xiao Yan, Shao-Kun Yang, De-Ying Cao, Qing Du, Xian-Rong Qi
As a potent therapeutic agent, small interfering RNA (siRNA) has been exploited to silence critical genes involved in tumor initiation and progression. However, development of a desirable delivery system is required to overcome the unfavorable properties of siRNA such as its high degradability, molecular size, and negative charge to help increase its accumulation in tumor tissues and promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic acids. In this study, we developed a new activatable cell-penetrating peptide (ACPP) that is responsive to an acidic tumor microenvironment, which was then used to modify the surfaces of siRNA-loaded liposomes...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28397487/design-and-proof-of-programmed-5-aminolevulinic-acid-prodrug-nanocarriers-for-targeted-photodynamic-cancer-therapy
#17
Jina Wu, Haijie Han, Qiao Jin, Zuhong Li, Huan Li, Jian Ji
5-Aminolevulinic acid (ALA), the precursor of photosensitizer protoporphyrin IX (PpIX), is a U.S. FDA-approved photodynamic therapeutic agent. However, realizing efficient delivery of ALA is still a big challenge as it is hydrophilic and cannot be recognized and selectively accumulated in tumor cells. In this study, matrix metalloproteinase-2 (MMP-2) and pH dual-sensitive ALA prodrug nanocarriers were constructed as a programmed delivery strategy for the targeted delivery of ALA. The nanocarriers were prepared by the co-modification of gold nanoparticles (AuNPs) with hydrazone-linked ALA and MMP-2-activatable cell-penetrating peptides (CPPs)...
April 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28393694/peptide-drug-conjugate-a-novel-drug-design-approach
#18
Liang Ma, Chao Wang, Zihao He, Biao Cheng, Ling Zheng, Kun Huang
More than 100 years ago, German physician Paul Ehrlich first proposed the concept of selectively delivering "magic bullets" to tumors through targeting agents. The targeting therapy with antibody-drug conjugates (ADCs) and peptide-drug conjugate (PDCs), which are usually composed of monoclonal antibodies or peptides, toxic payloads and cleavage/noncleavage linkers, has been extensively studied for decades. The conjugates enable selective delivery of cytotoxic payloads to target cells, which result in improved efficacy, reduced systemic toxicity and improved pharmacokinetics (PK)/pharmacodynamics (PD) compared with traditional chemotherapy...
April 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28389270/combination-of-valproic-acid-and-morpholino-splice-switching-oligonucleotide-produces-improved-outcomes-in-spinal-muscular-atrophy-patient-derived-fibroblasts
#19
Anna Farrelly-Rosch, Chew Ling Lau, Nitin Patil, Bradley J Turner, Fazel Shabanpoor
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality worldwide, is characterised by the homozygous loss of the survival motor neuron 1 (SMN1) gene. The consequent degeneration of spinal motor neurons and progressive atrophy of voluntary muscle groups results in paralysis and eventually premature infantile death. Humans possess a second nearly identical copy of SMN1, known as SMN2. However, SMN2 produces only 10-20% functional SMN protein due to aberrant splicing of its pre-mRNA that leads to the exclusion of exon 7...
April 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28388503/synthesis-and-in-vitro-evaluation-of-fluorescent-and-magnetic-nanoparticles-functionalized-with-a-cell-penetrating-peptide-for-cancer-theranosis
#20
Emiliana Perillo, Katel Hervé-Aubert, Emilie Allard-Vannier, Annarita Falanga, Stefania Galdiero, Igor Chourpa
We synthesized rationally designed multifunctional nanoparticles (NPs) composed of a superparamagnetic iron oxide nanoparticle (SPION) core, cyanine fluorescent dye emitting in far red, polyethylene glycol (PEG5000) coating, and the membranotropic peptide gH625, from the cell-penetrating peptides (CPP) family. The peptide sequence was enriched with an additional cysteine so it can be involved as a reactive moiety in a certain orientation- and sequence-specific coupling of the CPP to the PEG shell of the NPs...
March 29, 2017: Journal of Colloid and Interface Science
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