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Cell-penetrating peptides

Yuanyuan Yang, Qiling Chen, Siyu Li, Wen Ma, Guangyu Yao, Fei Ren, Zheng Cai, Peng Zhao, Guochao Liao, Jingyuan Xiong, Zhiqiang Yu
Despite the great achievements of nanomedicines made in cancer chemotherapy, precise tumor targeting and deep penetration are still major challenges. Many nanomedicines can only passively accumulate near leaky site of tumor vessels through the enhanced permeability and retention (EPR) effect and cannot reach the deep region of tumor. To improve the tumor targeting, penetration and retention efficiency, an iRGD-mediated and enzyme-induced precise targeting gold nanoparticles system (iRGD/AuNPs-A&C) was developed by simply coadministering a tumor-homing penetration peptide iRGD (CRGDKGPDC) with a legumain responsive aggregable gold nanoparticle (AuNPs-A&C)...
August 1, 2018: Journal of Biomedical Nanotechnology
Georgij Arapidi, Maria Osetrova, Olga Ivanova, Ivan Butenko, Tatjana Saveleva, Polina Pavlovich, Nikolay Anikanov, Vadim Ivanov, Vadim Govorun
Blood as connective tissue potentially contains evidence of all processes occurring within the organism, at least in trace amounts (Petricoin et al., 2006) [1]. Because of their small size, peptides penetrate cell membranes and epithelial barriers more freely than proteins. Among the peptides found in blood, there are both fragments of proteins secreted by various tissues and performing their function in plasma and receptor ligands: hormones, cytokines and mediators of cellular response (Anderson et al., 2002) [2]...
June 2018: Data in Brief
Balachandran Manavalan, Sathiyamoorthy Subramaniyam, Tae Hwan Shin, Myeong Ok Kim, Gwang Lee
Cell-penetrating peptides (CPPs) can enter cells as a variety of biologically active conjugates and have various biomedical applications. To offset the cost and effort of designing novel CPPs in laboratories, computational methods need to be developed to identify candidate CPPs before in vitro experimental studies. In this study, we developed a two-layer prediction framework for machine-learning-based prediction of cell-penetrating peptides (MLCPP). The first layer predicts whether a given peptide is a CPP or non-CPP, whereas the second layer predicts the uptake efficiency of the predicted CPPs...
June 12, 2018: Journal of Proteome Research
Ahmed Abdullah Al-Zaher, Rafael Moreno, Carlos Alberto Fajardo, Marcel Arias-Badia, Martí Farrera, Jana de Sostoa, Luis Alfonso Rojas, Ramon Alemany
To enhance adenovirus-mediated oncolysis, different approaches that tackle the selectivity, tumor penetration, and spreading potential of oncolytic adenoviruses have been reported. We have previously demonstrated that insertion of the internalizing Arginine-Glycine-Aspartic (iRGD) tumor-penetrating peptide at the C terminus of the fiber or transgenic expression of a secreted hyaluronidase can improve virus tumor targeting and spreading. Here we report a new oncolytic adenovirus ICOVIR17K-iRGD in which both modifications have been incorporated...
March 30, 2018: Molecular Therapy Oncolytics
Tereza Vaneckova, Kristyna Smerkova, Jan Zitka, David Hynek, Ondrej Zitka, Antonin Hlavacek, Frantisek Foret, Vojtech Adam, Marketa Vaculovicova
Upconversion nanoparticles (UCNPs) are an emerging class of optical materials with high potential in bioimaging due to practically no background signal and high penetration depth. Their excellent optical properties and easy surface functionalization make them perfect for conjugation with targeting ligands. In this work, capillary electrophoretic (CE) method with laser-induced fluorescence detection was used to investigate the behavior of carboxy-silica-UCNPs. Folic acid, targeting folate receptor overexpressed by wide variety of cancer cells, was used for illustrative purposes and assessed by CE under optimized conditions...
June 8, 2018: Electrophoresis
Lizhang Han, Ling Tang, Zheng Jiang, Yuquan Jiang
Glioma-Associated Oncogene Family Zinc Finger 2 (Gli2) seems to be the major nuclear effector of Sonic Hedgehog (SHH) signaling to regulate self-renewal and tumorigenic potential of Glioblastoma multiforme (GBM) cells. Three phosphorylated peptides derived from Gli2 were synthesized and combined with cell-penetrating peptide Tat-(47-57) (AYGRKKRRQRRR). Western Blot was applied to detect the phosphorylation level of Gli2 and cell division protein kinase 6 (CDK6) luciferase reporter was utilized to detect the transcriptional activator function of Gli2...
May 30, 2018: Neuropeptides
Melanie A Blevins, Caiguo Zhang, Lingdi Zhang, Hong Li, Xueni Li, David A Norris, Mingxia Huang, Rui Zhao
The carboxyl-terminal binding proteins (CtBP) are transcriptional co-repressors that regulate the expression of multiple epithelial-specific and pro-apoptotic genes. Overexpression of CtBP occurs in many human cancers where they promote the epithelial-to-mesenchymal transition, stem cell-like features, and cell survival, while knockdown of CtBP in tumor cells results in p53-independent apoptosis. CtBPs are recruited to their target genes by binding to a conserved PXDLS peptide motif present in multiple DNA-binding transcription factors...
June 7, 2018: Molecular Oncology
Chuan Hu, Xiaotong Yang, Rui Liu, Shaobo Ruan, Yang Zhou, Wei Xiao, Wenqi Yu, Chuanyao Yang, Huile Gao
Limited tumor targeting and poor penetration of nanoparticles are two major obstacles to improving the outcome of tumor therapy. Herein, coadministration of tumor-homing peptide iRGD and multistage-responsive penetrating nanoparticles for the treatment of breast cancer are reported. This multistage-responsive nanoparticle, IDDHN, was comprised of NO donor-modified hyaluronic acid shell (HN) and small-sized dendrimer, namely Dendri-Graft-L-Lysine conjugated with doxorubicin and indocyanine (IDD). The results showed that IDDHN could be degraded rapidly from about 330 nm to a smaller size that was in a size range of 35 nm to 150 nm (most at 35~60 nm) after hyaluronidase (HAase) incubation for 4 hours, in vitro cellular uptake demonstrated that iRGD could mediate more endocytosis of IDDHN into 4T1 cells, which was attributed to the overexpression of αvβ3 integrin receptor...
June 7, 2018: ACS Applied Materials & Interfaces
Xi He, Xinli Chen, Lisha Liu, Yu Zhang, Yifei Lu, Yujie Zhang, Qinjun Chen, Chunhui Ruan, Qin Guo, Chao Li, Tao Sun, Chen Jiang
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive malignancy with a five year survival rate of <5%. The aberrant expression of extracellular matrix (ECM) in the tumor stroma forms a compact physical barrier, which that leads to insufficient extravasation and penetration of nanosized therapies. To overcome the severe resistance of PDAC to conventional therapies, a sequentially triggered nanoparticle (aptamer/cell-penetrating peptide-camptothecin prodrug, i.e., Apt/CPP-CPTD NPs) with tumor penetration and intelligent drug release profile is designed...
May 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Avishai Shemesh, Kiran Kundu, Refael Peleg, Rami Yossef, Irena Kaplanov, Susmita Ghosh, Yana Khrapunsky, Orly Gershoni-Yahalom, Tatiana Rabinski, Adelheid Cerwenka, Roee Atlas, Angel Porgador
Proliferating cell nuclear antigen (PCNA) is considered as a hub protein and is a key regulator of DNA replication, repair, cell cycle control, and apoptosis. PCNA is overexpressed in many cancer types, and PCNA overexpression is correlated with cancer virulence. Membrane-associated PCNA is a ligand for the NKp44 (NCR2) innate immune receptor. The purpose of this study was to characterize the PCNA-binding site within NKp44. We have identified NKp44-derived linear peptide (pep8), which can specifically interact with PCNA and partly block the NKp44-PCNA interaction...
2018: Frontiers in Immunology
Jan K Marzinek, Nirmalya Bag, Roland G Huber, Daniel A Holdbrook, Thorsten Wohland, Chandra S Verma, Peter J Bond
During host cell infection by flaviviruses such as dengue and Zika, acidic pH within the endosome triggers a conformational change in the envelope protein on the outer surface of the virion. This results in exposure of the ~15 residue fusion peptide (FP) region, freeing it to induce fusion between the viral and endosomal membranes. A better understanding of the conformational dynamics of the FP in the presence of membranes, and the basis for its selectivity for anionic lipid species present within the endosome, would facilitate its therapeutic targetting with antiviral drugs and antibodies...
June 6, 2018: Journal of Chemical Theory and Computation
Zhili Yu, Junxiao Ye, Xing Pei, Lu Sun, Ergang Liu, Jianxin Wang, Yongzhuo Huang, Seung Jin Lee, Huining He
RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions in vivo and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides (CPP) to siRNA has become of great interest...
January 2018: Acta Pharmaceutica Sinica. B
Xiaobao Bi, Juan Yin, Xinya Hemu, Chang Rao, James P Tam, Chuan-Fa Liu
Backbone-cyclic proteins are of great scientific and therapeutic interest owing to their higher stability over their linear counterparts. Modification of such cyclic proteins at selected site would further enhance their versatility. Here we report a chemoenzymatic strategy to engineer site-selectively modified cyclic proteins by combining butelase-mediated macrocyclization with the genetic code expansion methodology. Using this strategy, we prepared a cyclic protein which was modified with biotin or a cell-penetrating peptide at a genetically incorporated non-canonical amino acid, making the cyclization-stabilized protein further amenable for site-specific immobilization and intracellular delivery...
June 5, 2018: Bioconjugate Chemistry
Zhian Jin, Pujie Wang, Jie Chen, Li He, Lijia Xiao, Kaisen Yong, Shenglin Deng, Lin Zhou
PURPOSE: C-end rule (CendR) peptides are found to enhance the penetration of chemotherapeutic agents into tumor cells, while GX1 is a peptide that homes to gastric cancer (GC) vasculature. This study aimed to synthesize a novel peptide GX1-RPAKPAR (GXC) and to explore the effect of GXC on sensitizing GC cells to chemotherapeutic agents. MATERIALS AND METHODS: Intracellular Adriamycin concentration analysis was applied to conform whether GXC peptide increases the penetration of chemotherapeutic agents into GC cells in vitro...
July 2018: Yonsei Medical Journal
Marta Pazo, Marisa Juanes, Irene Lostalé-Seijo, Javier Montenegro
Even for short peptides that are enriched in basic amino acids, the large chemical space that can be spanned by combinations of natural amino acids hinders the rational design of cell penetrating peptides. We here report on short oligoalanine scaffolds for the fine-tuning of peptide helicity in different media and the study of cell penetrating properties. This strategy allowed the extraction of the structure/activity features required for maximal membrane interaction and cellular penetration at minimal toxicity...
June 4, 2018: Chemical Communications: Chem Comm
Anbu Mozhi, Israr Ahmad, Qari Muhammad Kaleem, Ruslan G Tuguntaev, Ahmed Shaker Eltahan, Chen Wang, Rong Yang, Chan Li, Xing-Jie Liang
Mitochondria are considered the power house of cells where ATP is generated for cellular metabolism, and they also act as a crucial regulator of the intrinsic apoptosis pathway. During ATP synthesis, reactive oxygen species (ROS) are produced as secondary products. Overproduction of ROS can promote mitochondrial DNA mutation, dysfunction and depolarization of the mitochondrial membrane, ultimately resulting in cell death. Therefore, the destruction of mitochondria would be an effective therapeutic approach to kill malignant tumors...
May 31, 2018: International Journal of Pharmaceutics
Daehwan Park, Jin Yong Lee, Heui Kyoung Cho, Woo Jin Hong, Jisun Kim, Hyemyung Seo, Ikjang Choi, Youngbok Lee, Juhyeon Kim, Sun-Joon Min, So-Hyun Yoon, Jae Sung Hwang, Kwang Jin Cho, Jin Woong Kim
We herein propose a polymeric nanovehicle system that has the ability to remarkably improve cellular uptake and transdermal delivery. Cell-penetrating peptide-patchy deformable polymeric nanovehicles were fabricated by tailored co-assembly of amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL), mannosylerythritol lipid (MEL), and YGRKKRRQRRR-Cysteamine (TAT)-linked MEL. Using X-ray diffraction, differential scanning calorimetry, and nuclear magnetic resonance analyses, we revealed that the incorporation of MEL having an asymmetric alkyl chain configuration, was responsible for the deformable phase property of the vehicles...
May 30, 2018: Biomacromolecules
Tero A H Järvinen, Erkki Ruoslahti
Extracellular matrix (ECM) molecules play important roles in regulating processes such as cell proliferation, migration, differentiation and survival. Decorin (DCN) is a proteoglycan that binds to ("decorates") collagen fibrils in the ECM. DCN also interacts with multiple growth factors and their receptors, the most notable of these interactions being its inhibitory activity on transforming growth factor-β (TGF-β), the growth factor responsible for fibrosis formation. We have generated a recombinant, multi-functional, fusion-protein consisting of DCN as a therapeutic domain and vascular homing and cell penetrating peptide as a targeting vehicle...
May 30, 2018: British Journal of Pharmacology
Liberty François-Moutal, Erik T Dustrude, Yue Wang, Tatiana Brustovetsky, Angie Dorame, Weina Ju, Aubin Moutal, Samantha Perez-Miller, Nickolay Brustovetsky, Vijay Gokhale, May Khanna, Rajesh Khanna
We previously reported that destruction of the small ubiquitin-like modifier (SUMO) modification site in the axonal collapsin response mediator protein 2 (CRMP2) was sufficient to selectively decrease trafficking of the voltage-gated sodium channel NaV1.7 and reverse neuropathic pain. Here, we further interrogate the biophysical nature of the interaction between CRMP2 and the SUMOylation machiner affinity between CRMP2 and Ubc9. A heptamer peptide harboring CRMP2's SUMO motif, also bound with similar affinity to Ubc9 and disrupted the CRMP2-Ubc9 interaction in a concentration-dependent manner...
May 25, 2018: Pain
Lauriane N Roux, Isabelle Petit, Romain Domart, Jean-Paul Concordet, Jieqiong Qu, Huiqing Zhou, Alain Joliot, Olivier Ferrigno, Daniel Aberdam
Heterozygous PAX6 gene mutations leading to haploinsufficiency are the main cause of congenital aniridia, a rare and progressive panocular disease characterized by reduced visual acuity. Up to 90% of patients suffer from aniridia-related keratopathy (ARK), caused by a combination of factors including limbal epithelial stem cell (LSC) deficiency, impaired healing response and abnormal differentiation of the corneal epithelium. It usually begins in the first decade of life, resulting in recurrent corneal erosions, sub-epithelial fibrosis and corneal opacification...
May 29, 2018: Stem Cells
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