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Cell-penetrating peptides

Stefan Braun, Šárka Pokorná, Radek Šachl, Martin Hof, Heiko Heerklotz, Maria Hoernke
The mode of action of membrane-active molecules such as antimicrobial, anticancer, cell penetrating, and fusion peptides and their synthetic mimics, transfection agents and drug permeation enhancers, biological signaling molecules (e.g., quorum sensing), involves either the general or local destabilization of the target membrane or the formation of defined, rather stable pores. Some effects aim at killing the cell, others need to be limited in space and time to avoid serious damage. Biological tests reveal translocation of compounds and cell death but do not provide a detailed, mechanistic, and quantitative understanding of the modes of action and their molecular basis...
December 15, 2017: ACS Nano
Rajendra Narayan Mitra, Min Zheng, Ellen R Weiss, Zongchao Han
Retinitis pigmentosa (RP) is a group of inherited retinal degenerative conditions and a leading cause of irreversible blindness. 25%-30% of RP cases are caused by inherited autosomal dominant (ad) mutations in the rhodopsin (Rho) protein of the retina, which impose a barrier for developing therapeutic treatments for this genetically heterogeneous disorder, as simple gene replacement is not sufficient to overcome dominant disease alleles. Previously, we have explored using the genomic short-form of Rho (sgRho) for gene augmentation therapy of RP in a Rho knockout mouse model...
December 5, 2017: Biomaterials
I W Hamley
This review is aimed to provide a concise yet extensive survey of key short bioactive peptide sequences for a range of applications ranging from biomaterials development to peptides with therapeutic uses. The following are considered: cell adhesion motifs, structural peptides, cell-penetrating and tumor-homing peptides, antimicrobial peptides, peptide hormones, growth factors and matrix metalloprotease substrates, neuropeptides, amyloid peptides, antioxidant peptides, peptide affinity tags, anticancer peptides, and others...
December 11, 2017: Chemical Reviews
Steven Samuels, Zainab Alwan, Marceline Egnin, Jessie Jaynes, Terry D Connell, Gregory C Bernard, Toufic Nashar
Despite advancements in our understanding of HIV-1 pathogenesis, critical virus components for immunity, vaccines trials, and drugs development, challenges remain in the fight against HIV-1. Of great importance is the inhibitory function of microbicidal cell penetrating peptides and bacterial toxins that interfere with production and neutralize infection of HIV-1 particles. We demonstrate that the neutralizing activity of a cationic 18 amino acids peptide, is similar to a broadly neutralizing human antibody, and inhibits production of two HIV-1 strains in human cell lines...
October 2017: Journal of AIDS & Clinical Research
Junghee Park, Ji-Hye Han, Seung-Hyun Myung, Young-Woo Seo, Tae-Hyoung Kim
The mitochondrial targeting domain (MTD) of Noxa has necrosis-inducing activity when conjugated with cell-penetrating peptide (CPP). In this study, we report another MTD-like motif, B1MLM, found in BNIP1, a pro-apoptotic BH3-only protein found in the endoplasmic reticulum membrane. The B1MLM peptide, conjugated with CPP, induced necrosis in a way similar to that of R8:MTD. R8:B1MLM caused an intracellular calcium spike, mitochondrial reactive oxygen species generation, and mitochondrial fragmentation. The cytosolic calcium spike was likely due to the opening of the mitochondrial permeability transition pore...
December 5, 2017: Biochemical and Biophysical Research Communications
Jianguo Jia, Yang Zhang, Min Zheng, Changfu Shan, Huicheng Yan, Wenyu Wu, Xuan Gao, Bo Cheng, Weisheng Liu, Yu Tang
The postsynthetic-modified nanoscale metal-organic framework (NMOF) probes selected as potential drug delivery platforms and photodynamic therapy agents to fulfill the effective and safe treatment of neoplastic diseases have attracted increasing attention recently. Herein, a Eu(III)-based NMOF probe elaborately postsynthetically modified with a β-diketonate two-photon-absorbing (TPA) ligand is rationally designed and further functionalized by assembling the photosensitizer molecule (methylene blue, MB) in the pores and a cyclic peptide targeting motif on the surface of the NMOF, which could achieve highly efficient near-infrared (NIR)-triggered and -targeted photodynamic therapy (PDT)...
December 8, 2017: Inorganic Chemistry
Chitrak Gupta, Blake Mertz
Cell-penetrating peptides (CPPs) can be potentially used in targeted delivery of therapeutic cargoes. However, their conformation in solution is poorly understood. We employed molecular dynamics simulations to probe the structural fluctuations of an anionic CPP, pH Low Insertion Peptide (pHLIP), in solution to determine the effects of modifications to selected residues on the structure of pHLIP. Two types of modifications were tested: (1) protonation of aspartic acid residues and (2) point mutations known to affect the acid sensitivity of pHLIP...
November 30, 2017: ACS Omega
Peter Bannas, Julia Hambach, Friedrich Koch-Nolte
Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv)...
2017: Frontiers in Immunology
Kaido Kurrikoff, Kadi-Liis Veiman, Kadri Künnapuu, Elin Madli Peets, Tõnis Lehto, Ly Pärnaste, Piret Arukuusk, Ülo Langel
Non-viral gene delivery systems have gained considerable attention as a promising alternative to viral delivery to treat diseases associated with aberrant gene expression. However, regardless of extensive research, only a little is known about the parameters that underline in vivo use of the nanoparticle-based delivery vectors. The modest efficacy and low safety of non-viral delivery are the two central issues that need to be addressed. We have previously characterized an efficient cell penetrating peptide, PF14, for in vivo applications...
December 6, 2017: Scientific Reports
Terese Soudah, Maxim Mogilevsky, Rotem Karni, Eylon Yavin
Efficient delivery of oligonucleotides still remains a challenge in the field of oligonucleotide based therapy. Peptide nucleic acid (PNA), a DNA analogue that is typically synthesized by solid phase peptide chemistry, has been conjugated to a variety of cell penetrating peptides (CPP) as a means of improving its cellular uptake. These CPPs typically deliver their cargoes into cells by an endosomal-dependent mechanism resulting in lower bioavailability of the cargo. Herein, we designed and synthesized PNA-peptide conjugates as splice switching oligonucleotides (SSO) targeting the Mnk2 gene, a therapeutic target in cancer...
December 6, 2017: Bioconjugate Chemistry
Xing Guo, Lin Wang, Kayla Duval, Jing Fan, Shaobing Zhou, Zi Chen
Trans-activating transcriptional activator (TAT), a cell-penetrating peptide, is extensively used for facilitating cellular uptake and nuclear targeting of drug delivery systems. However, the positively charged TAT peptide strongly interacts with serum components and undergoes substantial phagocytosis by the reticuloendothelial system, causing a short blood circulation in vivo. In this work, an acid-active tumor targeting nanoplatform DA-TAT-PECL is developed to inhibit the nonspecific interactions of TAT in the bloodstream...
December 6, 2017: Advanced Materials
Shakir Hasan, Nikhil Nitin Kulkarni, Arni Asbjarnarson, Irena Linhartova, Radim Osicka, Peter Sebo, Gudmundur H Gudmundsson
Airway epithelium restricts penetration of inhaled pathogens into the underlying tissue and plays a crucial role in innate immune defense against respiratory infections. The whooping cough agent, Bordetella pertussis, adheres to ciliated cells of human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We have examined the impact of B. pertussis infection and of adenylate cyclase toxin (CyaA) action on the functional integrity of air-liquid interface (ALI)-cultured human bronchial epithelial cells...
December 4, 2017: Infection and Immunity
Mingxiu Lv, Mengwei Wang, Kui Lu, Bingchao Duan, Yufen Zhao
CA-TAT, a novel peptide analog, was modified at the N-terminus of TAT (47-57), the cell-penetrating peptide transacting activator of transcription, by attaching cecropin A (1-7). CA-TAT, TAT (47-57), and cecropin A (1-7) were synthesized using standard Fmoc solid-phase peptide synthesis procedures, purified using reversed-phase high performance liquid chromatography (RP-HPLC), and characterized using ESI-MS. CA-TAT demonstrated antibacterial activities against bacteria with low hemolysis (MHC>128μM). The minimum inhibitory concentration (MIC) values of CA-TAT were in the range of 1-16μM, which completely inhibited both gram-positive and gram-negative bacteria...
November 29, 2017: International Journal of Biological Macromolecules
Cristina de la Torre, Leticia Domínguez-Berrocal, Jose R Murguía, M Dolores Marcos, Ramón Martínez-Máñez, Jeronimo Bravo, Felix Sancenón
Apoptotic signalling pathway is altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Acα interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumour cells. Very recently a short peptide (C9h) known to disrupt caspase-9/PP2Acα interaction with subsequent apoptosis induction was described. Here we prepared two sets of mesoporous silica nanoparticles loaded with safranin O (S2) or with C9h peptide (S4) and functionalized with -polylysine as capping unit...
November 29, 2017: Chemistry: a European Journal
Ajmeeta Sangtani, Eleonora Petryayeva, Miao Wu, Kimihiro Susumu, Eunkeu Oh, Alan L Huston, Guillermo Lasarte-Aragones, Igor L Medintz, W Russ Algar, James B Delehanty
Nanoparticle (NP)-mediated drug delivery (NMDD) has emerged as a novel method to overcome the limitations of traditional systemic delivery of therapeutics, including the controlled release of the NP-associated drug cargo. Currently, our most advanced understanding of how to control NP-associated cargos is in the context of soft nanoparticles (e.g., liposomes), but less is known about controlling the release of cargos from the surface of hard NPs (e.g., gold NPs). Here we employ a semiconductor quantum dot (QD) as a prototypical hard NP platform and use intracellularly- triggered actuation to achieve spatiotemporal control of drug release and modulation of drug efficacy...
November 30, 2017: Bioconjugate Chemistry
Chul-Kyu Park, Yong Ho Kim, Suhyun Hwangbo, Hoonsung Cho
Photodynamic therapy (PDT) is a promising alternative therapy that could be used as an adjunct to chemotherapy and surgery for cancer, and works by destroying tissue with visible light in the presence of a photosensitizer (PS) and oxygen. The PS should restrict tissue destruction only to the tumor and be activated by light of a specific wavelength; both of these properties are required. Arginine-rich peptides, such as cell-penetrating peptides, have membrane-translocating and nuclear-localizing activities, which have led to their application in various drug delivery modalities...
2017: International Journal of Nanomedicine
Shu-Wen He, Guang-Hua Wang, Bin Yue, Shun Zhou, Min Zhang
Tissue factor pathway inhibitor (TFPI)-1 is well known for its role as an inhibitor of blood coagulation. Several studies have demonstrated that the C-terminal peptides of TFPI-1 are active against a broad spectrum of microorganisms. In a previous study, we found that TO17 (with 17 amino acids), a TFPI-1 C-terminal peptide from red drum (Sciaenops ocellatus), was active against Edwardsiella tarda. In the present study, we investigated further the antimicrobial spectrum, action mode, as well as the immunostimulatory property of TO17...
November 25, 2017: Fish & Shellfish Immunology
Lemmuel L Tayo
The emergence of different nanoparticles (NPs) has made a significant revolution in the field of medicine. Different NPs in the form of metallic NPs, dendrimers, polymeric NPs, carbon quantum dots and liposomes have been functionalized and used as platforms for intracellular delivery of biomolecules, drugs, imaging agents and nucleic acids. These NPs are designed to improve the pharmacokinetic properties of the drug, improve their bioavailability and successfully surpass physiological or pathological obstacles in the biological system so that therapeutic efficacy is achieved...
November 25, 2017: Biophysical Reviews
Astrid Walrant, Sébastien Cardon, Fabienne Burlina, Sandrine Sagan
Living organisms have to maintain a stable balance in molecules and ions in the changing environment in which they are living, a process known as homeostasis. At the level of cells, the plasma membrane has a major role in homeostasis, since this hydrophobic film prevents passive diffusion of large and hydrophilic molecules between the extracellular and intracellular milieu. Living organisms have evolved with highly sophisticated transport systems to control exchanges across this barrier: import of nutrients and fuel essential for their survival; recognition of chemical or physical messengers allowing information interchanges with surrounding cells...
November 27, 2017: Accounts of Chemical Research
Filipa Gonçalves, Tarsila G Castro, Eugénia Nogueira, Ricardo Pires, Carla Silva, Artur Ribeiro, Artur Cavaco-Paulo
Cell-penetrating peptides (CPPs) have been applied as novel transport systems with the ability to facilitate the delivery of peptides, proteins, and oligonucleotides into cells. Herein, we designed different fusion proteins composed by pig odorant binding protein (OBP-I) and three CPPs, namely Tat, pVEC and Pep-1. A new methodology using liposomes as reservoirs and OBP:CPPs as carriers was developed as an advanced system to capture odorant molecules. 1-aminoanthracene (1-AMA) was used as a model molecule to evaluate the transduction ability of OBP:CPPs into the reservoirs...
November 10, 2017: Colloids and Surfaces. B, Biointerfaces
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