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R9 peptide

N Sanoj Rejinold, Yunho Han, Jisang Yoo, Hae Yong Seok, Ji Ho Park, Yeu-Chun Kim
This work aimed at formulating paclitaxel (PTX) loaded cell penetrating peptide (CPP) coated Mn doped ZnS nanoparticles (Mn:ZnS NPs) for improved anti-cancer efficacy in vitro and in vivo. The developed PTX loaded Mn:ZnS NPs with different CPPs (PEN, pVEC and R9) showed enhanced anti-cancer effect compared to bare PTX, which has been validated by MTT assay followed by apoptosis assay and DNA fragmentation analysis. The in vivo bio-distribution and anti-cancer efficacy was studied on breast cancer xenograft model showing maximum tumor localization and enhanced therapeutic efficacy with R9 coated Mn:ZnS NPs (R9:Mn:ZnS NPs) and was confirmed by H/E staining...
January 30, 2018: Scientific Reports
Qianqian Kang, Zhaolin Sun, Zhiyuan Zou, Ming Wang, Qiuyan Li, Xiaoxiang Hu, Ning Li
Cell-penetrating peptides (CPPs) have been increasingly used to deliver various molecules, both in vitro and in vivo. However, there are no reports of CPPs being used in porcine fetal fibroblasts (PFFs). The increased use of transgenic pigs for basic research and biomedical applications depends on the availability of technologies for efficient genetic-modification of PFFs. Here, we report that three CPPs (CPP5, TAT, and R9) can efficiently deliver active Cre recombinase protein into PFFs via an energy-dependent endocytosis pathway...
2018: PloS One
Xiao Xiao, Xingxing Wang, Yuqi Wang, Tianren Yu, Lei Huang, Lei Chen, Jinbo Li, Chenyu Zhang, Yan Zhang
Targeted delivery of microRNA (miRNA) mimics into specific cells/tissues and real-time monitoring on the biological function of delivered miRNA mimics at molecular level represent two major challenges in the development of miRNA-based therapeutics. Here we report a highly efficient method to address these two challenges simultaneously by using the self-assembled nanocomplex formed by miRNA mimics with a multi-functional peptide conjugate. Using the nanocomplex formed by tumor-suppressive miR-34a and the multi-functional peptide conjugate FA-R9-FPcas3 , we demonstrated the highly efficient and target-selective delivery of miR-34a into HeLa cells and tumors...
February 9, 2018: Chemistry: a European Journal
Nian-Qiu Shi, Yan Li, Yong Zhang, Nan Shen, Ling Qi, Shu-Ran Wang, Xian-Rong Qi
Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R9 -liposome-based cargo delivery for tumor targeting...
December 6, 2017: ACS Applied Materials & Interfaces
Jianru Pan, Lunqiao Wu, Huocong He, Lijuan Chen, Ying Su, Lingling Li, Shutao Liu
The fusion of cell permeable peptide TAT and bifunctional antioxidant enzymes, GST (Glutathione sulfur transferase)-TAT-SOD1 (Cu, Zn superoxide dismutase), is an intracellular superoxide scavenger. Compared with SOD1-TAT, GST-TAT-SOD1 has better protective effect on oxidative damage but less transduction efficiency. A novel cell permeable bifunctional antioxidant enzymes with the fusion of GST, SOD1 and polyarginine R9 was constructed for higher transduction efficiency. The full nucleotide sequence of SOD1-R9 was synthesized and inserted into the prokaryotic expression vector pGEX-4T-1 with the GST tag...
May 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Sara Macchi, Riccardo Nifosì, Giovanni Signore, Sebastiano Di Pietro, Claudia Boccardi, Francesca D'Autilia, Fabio Beltram, Francesco Cardarelli
By a combination of UV-Vis analyses, NMR-based diffusion measurements and MD simulations we have demonstrated for the first time that the HIV-1 Tat arginine-rich peptide (Tat11 ) is able to self-aggregate in both its fluorescently labeled and unlabeled variants. We propose Tat11 dimerization as the dominant aggregation process and show that the associated equilibrium constant increases ten-fold by labeling with the standard TAMRA dye. Also, we extend similar conclusions to other cationic cell penetrating peptides (CPPs), such as Antennapedia (Ant) and nona-arginine (R9)...
September 13, 2017: Physical Chemistry Chemical Physics: PCCP
Takayuki Hattori, Koyo Okitsu, Norikazu Yamazaki, Nobumichi Ohoka, Norihito Shibata, Takashi Misawa, Masaaki Kurihara, Yosuke Demizu, Mikihiko Naito
We designed and synthesized hybrid molecules for a protein knockdown method based on the recognition of a His-tag fused to a protein of interest (POI). The synthesized target protein degradation inducers contained three functional moieties: a His-tag ligand (nickel nitrilotriacetic acid [Ni-NTA]), an E3 ligand (bestatin [BS] or MV1), and a carrier peptide (Tat or nonaarginine [R9]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, and MV1-R9-Ni-NTA, efficiently degraded His-tagged cellular retinoic acid binding protein 2 via the ubiquitin-proteasome system (UPS)...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
Yingqin Hou, Yaoyi Wang, Ruijue Wang, Weier Bao, Xiaobo Xi, Yunlong Sun, Shengtao Yang, Wei Wei, Hua Lu
To improve the therapeutic index of cisplatin (CDDP), we present here a new paradigm of drug-induced self-assembly by harnessing phosphato-platinum complexation. Specifically, we show that a phosphato-platinum cross-linked micelle (PpY/Pt) can be generated by using a block copolymer methoxy-poly(ethylene glycol)-block-poly(l-phosphotyrosine) (mPEG-b-PpY). Coating of PpY/Pt with a R9-iRGD peptide by simple mixing affords a targeting micelle with near neutral-charged surface (iPpY/Pt). The micelles feature in well-controlled sizes below 50 nm and high stability under physiological conditions, and can withstand various environmental stresses...
May 16, 2017: ACS Applied Materials & Interfaces
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...
June 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
J Mesken, A Iltzsche, D Mulac, K Langer
Gene therapy bears great potential for the cure of a multitude of human diseases. Research efforts focussed on the use of viral delivery vectors in the past decades, neglecting non-viral gene therapies of physical or chemical origin due to low transfection efficiency. However, side effects such as activation of oncogenes and inflammatory reactions upon immune cell activation are major obstacles impeding the clinical applicability of viral gene therapy vectors. The aim of this study was the development of a non-viral gene delivery system based on plasmid-loaded human serum albumin nanoparticles, which are biocompatible, biodegradable, and non-toxic in relevant concentrations...
March 6, 2017: International Journal of Pharmaceutics
A Özgül Tezgel, Paejonette Jacobs, Coralie M Backlund, Janice C Telfer, Gregory N Tew
The use of proteins as biological tools and therapeutic agents is limited due to the fact that proteins do not effectively cross the plasma membrane of cells. Here, we report a novel class of protein transporter molecules based on protein transduction domain mimics (PTDMs) synthesized via ring opening metathesis polymerization (ROMP). The PTDMs reported here were specifically inspired by amphiphilic peptides known to deliver functional proteins into cells via noncovalent interactions between the peptide and the cargo...
March 13, 2017: Biomacromolecules
Ugutz Unzueta, Joaquin Seras-Franzoso, María Virtudes Céspedes, Paolo Saccardo, Francisco Cortés, Fabián Rueda, Elena Garcia-Fruitós, Neus Ferrer-Miralles, Ramon Mangues, Esther Vázquez, Antonio Villaverde
Bacterial inclusion bodies are non-toxic, mechanically stable and functional protein amyloids within the nanoscale size range that are able to naturally penetrate into mammalian cells, where they deliver the embedded protein in a functional form. The potential use of inclusion bodies in protein delivery or protein replacement therapies is strongly impaired by the absence of specificity in cell binding and penetration, thus preventing targeting. To address this issue, we have here explored whether the genetic fusion of two tumor-homing peptides, the CXCR4 ligands R9 and T22, to an inclusion body-forming green fluorescent protein (GFP), would keep the interaction potential and the functionality of the fused peptides and then confer CXCR4 specificity in cell binding and further uptake of the materials...
January 6, 2017: Nanotechnology
Adam B Edwards, Ryan S Anderton, Neville W Knuckey, Bruno P Meloni
In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with D-amino acids (R9D-NH2)...
February 2017: Molecular and Cellular Biochemistry
Salma Teimoori, Watee Seesuay, Surasak Jittavisutthikul, Urai Chaisri, Nitat Sookrung, Jaslan Densumite, Nawannaporn Saelim, Monrat Chulanetra, Santi Maneewatch, Wanpen Chaicumpa
A direct acting anti-Ebola agent is needed. VP40, a conserved protein across Ebolavirus (EBOV) species has several pivotal roles in the virus life cycle. Inhibition of VP40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. In this study, cell penetrable human scFvs (HuscFvs) that bound to EBOV VP40 were produced by phage display technology. Gene sequences coding for VP40-bound-HuscFvs were subcloned from phagemids into protein expression plasmids downstream to a gene of cell penetrating peptide, i...
October 14, 2016: Biochemical and Biophysical Research Communications
Jennifer Y Xie, Lindsey A Chew, Xiaofang Yang, Yuying Wang, Chaoling Qu, Yue Wang, Lauren M Federici, Stephanie D Fitz, Matthew S Ripsch, Michael R Due, Aubin Moutal, May Khanna, Fletcher A White, Todd W Vanderah, Philip L Johnson, Frank Porreca, Rajesh Khanna
Uncoupling the protein-protein interaction between collapsin response mediator protein 2 (CRMP2) and N-type voltage-gated calcium channel (CaV2.2) with an allosteric CRMP2-derived peptide (CBD3) is antinociceptive in rodent models of inflammatory and neuropathic pain. We investigated the efficacy, duration of action, abuse potential, and neurobehavioral toxicity of an improved mutant CRMP2 peptide. A homopolyarginine (R9)-conjugated CBD3-A6K (R9-CBD3-A6K) peptide inhibited the CaV2.2-CRMP2 interaction in a concentration-dependent fashion and diminished surface expression of CaV2...
September 2016: Pain
Sabrina Sharmin, Md Zahidul Islam, Mohammad Abu Sayem Karal, Sayed Ul Alam Shibly, Hideo Dohra, Masahito Yamazaki
The cell-penetrating peptide R9, an oligoarginine comprising nine arginines, has been used to transport biological cargos into cells. However, the mechanisms underlying its translocation across membranes remain unclear. In this report, we investigated the entry of carboxyfluorescein (CF)-labeled R9 (CF-R9) into single giant unilamellar vesicles (GUVs) of various lipid compositions and the CF-R9-induced leakage of a fluorescent probe, Alexa Fluor 647 hydrazide (AF647), using a method developed recently by us...
August 2, 2016: Biochemistry
Ji Woong Lee, Ji-Ae Park, Yong Jin Lee, Un Chol Shin, Suhng Wook Kim, Byung Il Kim, Sang Moo Lim, Gwang Il An, Jung Young Kim, Kyo Chul Lee
Most studies of radiolabeled arginine-glycine-aspartic acid (RGD) peptides have shown in vitro affinity for integrin ανβ3, allowing for the targeting of receptor-positive tumors in vivo. However, major differences have been found in the pharmacokinetic profiles of different radiolabeled RGD peptide analogs. The purposes of this study were to prepare (64)Cu-DOTA-gluco-E[c(RGDfK)]2 (R8), (64)Cu-NOTA-gluco-E[c(RGDfK)]2 (R9), and (64)Cu-NODAGA-gluco-E[c(RGDfK)]2 (R10) and compare their pharmacokinetics and tumor imaging properties using small-animal positron emission tomography (PET)...
August 2016: Cancer Biotherapy & Radiopharmaceuticals
Ken Saito, Hidekazu Iioka, Chie Kojima, Mikako Ogawa, Eisaku Kondo
p14(ARF) is one of the major tumor suppressors conventionally identified both as the mdm2-binding molecule restoring p53 function in the nucleus, and as a nucleophosmin-binding partner inside the nucleolous to stabilize ribosomal RNA. However, its recently reported mitochondrial localization has pointed to novel properties as a tumor suppressor. At the same time, functional peptides are gaining much attention in nanomedicine for their in vivo utility as non-invasive biologics. We previously reported the p14(ARF) -specific peptide that restored the sensitivity to gefitinib on the gefitinib-resistant lung cancer cells...
September 2016: Cancer Science
Diego Milani, Vince W Clark, Jane L Cross, Ryan S Anderton, Neville W Knuckey, Bruno P Meloni
BACKGROUND: We recently reported that poly-arginine peptides have neuroprotective properties both in vitro and in vivo. In cultured cortical neurons exposed to glutamic acid excitotoxicity, we demonstrated that neuroprotective potency increases with polymer length plateauing at R15 to R18 (R = arginine resides). In an in vivo study in rats, we also demonstrated that R9D (R9 peptide synthesised with D-isoform amino acids) administered intravenously at a dose of 1000 nmol/kg 30 min after permanent middle cerebral artery occlusion (MCAO) reduces infarct volume...
May 3, 2016: BMC Neuroscience
Nabil A Alhakamy, Prajnaparamita Dhar, Cory J Berkland
Noncovalent complexation of plasmid DNA (pDNA) with cell-penetrating peptides (CPPs) forms relatively large complexes with poor gene expression. Yet, condensing these CPP-pDNA complexes via addition of calcium chloride produces small and stable nanoparticles with high levels of gene expression. This simple formulation offered high transfection efficiency and negligible cytotoxicity in HEK-293 (a virus-immortalized kidney cell) and A549 (a human lung cancer cell line). Small changes in CPP charge type, charge spacing, and hydrophobicity were studied by using five arginine-rich CPPs: the well-known hydrophilic polyarginine R9 peptide, a hydrophilic RH9 peptide, and three amphiphilic peptides (RA9, RL9, and RW9) with charge distributions that favor membrane penetration...
March 7, 2016: Molecular Pharmaceutics
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