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https://www.readbyqxmd.com/read/28107705/incorporation-of-antimicrobial-peptides-in-nanostructured-lipid-membrane-mimetic-bilayer-cubosomes
#1
Thomas G Meikle, Alexandru Zabara, Lynne J Waddington, Frances Separovic, Calum J Drummond, Charlotte E Conn
The inverse bicontinuous lipidic cubic phase offers a simple and robust membrane mimetic with the ability to encapsulate peptides, potentially increasing bioavailability, while also offering a platform from which functionalized, targeted nanoparticles can be developed. Herein we have investigated the use of a number of cubic phase nanoparticle systems with encapsulated antimicrobial peptides gramicidin A', melittin, and alamethicin. The optimal peptide loading ranges, over which cubic symmetry was retained, were determined using small angle X-ray scattering...
January 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28102001/evaluation-of-the-hybrid-resolution-pace-model-for-the-study-of-folding-insertion-and-pore-formation-of-membrane-associated-peptides
#2
Michael D Ward, Shivangi Nangia, Eric R May
The PACE force field presents an attractive model for conducting molecular dynamics simulations of membrane-protein systems. PACE is a hybrid model, in which lipids and solvents are coarse-grained consistent with the MARTINI mapping, while proteins are described by a united atom model. However, given PACE is linked to MARTINI, which is widely used to study membranes, the behavior of proteins interacting with membranes has only been limitedly examined in PACE. In this study, PACE is used to examine the behavior of several peptides in membrane environments, namely WALP peptides, melittin and influenza hemagglutinin fusion peptide (HAfp)...
January 19, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28071737/efficient-biosynthesis-of-a-cecropin-a-melittin-mutant-in-bacillus-subtilis-wb700
#3
Shengyue Ji, Weili Li, Abdul Rasheed Baloch, Meng Wang, Hengxin Li, Binyun Cao, Hongfu Zhang
The efficient production of antimicrobial peptides (AMPs) for clinical applications has attracted the attention of the scientific community. To develop a novel microbial cell factory for the efficient biosynthesis of a cecropin A-melittin mutant (CAM-W), a recombinant Bacillus subtilis WB700 expression system was genetically modified with a novel vector, including a fusion gene encoding CAM-W, the autoprotease EDDIE and the signal peptide SacB under the control of the maltose-inducible promoter Pglv. A total of 159 mg of CAM-W was obtained from 1 L of fermentation supernatant...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28024889/towards-prostate-cancer-gene-therapy-development-of-a-chlorotoxin-targeted-nanovector-for-toxic-melittin-gene-delivery
#4
Zahra Tarokh, Hossein Naderi-Manesh, Mahboobeh Nazari
Prostate cancer is the second leading cause of death due to cancer in men. Owing to shortcomings in the current treatments, other therapies are being considered. Toxic gene delivery is one of the most effective methods for cancer therapy. Cationic polymers are able to form stable nanoparticles via interaction with nucleic acids electrostatically. Branched polyethylenimine that contains amine groups has notable buffering capacity and the ability to escape from endosome through the proton sponge effect. However, the cytotoxicity of this polymer is high, and modification is one of the applicable strategies to overcome this problem...
December 23, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28013523/hemolytic-activity-of-antimicrobial-peptides
#5
Alberto Oddo, Paul R Hansen
For antimicrobial peptides to be interesting for systemic applications, they must show low toxicity against erythrocytes. In this chapter, we describe a protocol for measuring the ability of AMPs to lyse human red blood cells, using melittin as positive control.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28004569/strategies-for-the-activation-and-release-of-the-membranolytic-peptide-melittin-from-liposomes-using-endosomal-ph-as-a-trigger
#6
Erik Oude Blenke, Malgorzata Sleszynska, Martijn Evers, Gert Storm, Nathaniel I Martin, Enrico Mastrobattista
Endosomolytic peptides are often coupled to drug delivery systems to enhance endosomal escape, which is crucial for the delivery of macromolecular drugs that are vulnerable to degradation in the endolysosomal pathway. Melittin is a 26 amino acid peptide derived from bee venom that has a very high membranolytic activity. However, such lytic peptides also impose a significant safety risk when applied in vivo as they often have similar activity against red blood cells and other non-target cell membranes. Our aim is to control the membrane-disrupting capacity of these peptides in time and space by physically constraining them to a nanocarrier surface in such a way that they only become activated when delivered inside acidic endosomes...
December 22, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/27986445/nadph-oxidase-4-regulates-vascular-inflammation-in-aging-and-atherosclerosis
#7
Andrey Lozhkin, Aleksandr E Vendrov, Hua Pan, Samuel A Wickline, Nageswara R Madamanchi, Marschall S Runge
We recently reported that increased NADPH oxidase 4 (NOX4) expression and activity during aging results in enhanced cellular and mitochondrial oxidative stress, vascular inflammation, dysfunction, and atherosclerosis. The goal of the present study was to elucidate the molecular mechanism(s) for these effects and determine the importance of NOX4 modulation of proinflammatory gene expression in mouse vascular smooth muscle cells (VSMCs). A novel peptide-mediated siRNA transfection approach was used to inhibit Nox4 expression with minimal cellular toxicity...
December 14, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27894306/first-phase-i-human-clinical-trial-of-a-killed-whole-hiv-1-vaccine-demonstration-of-its-safety-and-enhancement-of-anti-hiv-antibody-responses
#8
Eunsil Choi, Chad J Michalski, Seung Ho Choo, Gyoung Nyoun Kim, Elizabeth Banasikowska, Sangkyun Lee, Kunyu Wu, Hwa-Yong An, Anthony Mills, Stefan Schneider, U Fritz Bredeek, Daniel R Coulston, Shilei Ding, Andrés Finzi, Meijuan Tian, Katja Klein, Eric J Arts, Jamie F S Mann, Yong Gao, C Yong Kang
BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus...
November 28, 2016: Retrovirology
https://www.readbyqxmd.com/read/27888461/inhibitory-effects-of-bee-venom-and-its-components-against-viruses-in-vitro-and-in-vivo
#9
Md Bashir Uddin, Byeong-Hoon Lee, Chamilani Nikapitiya, Jae-Hoon Kim, Tae-Hwan Kim, Hyun-Cheol Lee, Choul Goo Kim, Jong-Soo Lee, Chul-Joong Kim
Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A2 (PLA2), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV)...
December 2016: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/27877159/efficacy-of-antibacterial-peptides-against-peptide-resistant-mrsa-is-restored-by-permeabilization-of-bacteria-membranes
#10
Joshua Ravensdale, Zachary Wong, Frances O'Brien, Keith Gregg
Clinical application of antimicrobial peptides (AMPs), as with conventional antibiotics, may be compromised by the development of bacterial resistance. This study investigated AMP resistance in methicillin resistant Staphylococcus aureus, including aspects related to the resilience of the resistant bacteria toward the peptides, the stability of resistance when selection pressures are removed, and whether resistance can be overcome by using the peptides with other membrane-permeabilising agents. Genotypically variant strains of S...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27808347/clinical-efficacy-of-melittin-in-the-treatment-of-cats-infected-with-the-feline-immunodeficiency-virus
#11
Anja D Hartmann, Natalie Wilhelm, Volker Erfle, Katrin Hartmann
OBJECTIVE: The bee venom melittin shows an antiviral efficacy against the human immunodeficiency virus in cell culture. It was shown to be non-toxic for cats. Aim of this pilot study was to investigate the clinical efficacy and side-effects of melittin in cats naturally infected with feline immunodeficiency virus (FIV). MATERIAL AND METHODS: The study was performed as a prospective, placebo-controlled double-blinded trial. Twenty cats were included, of which 10 cats each were treated with either melittin (500 µg/kg body weight) or phosphate-buffered saline (placebo) subcutaneously twice per week...
December 5, 2016: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
https://www.readbyqxmd.com/read/27788004/characterizing-and-controlling-the-loading-and-release-of-cationic-amphiphilic-peptides-onto-and-from-peg-stabilized-lipodisks
#12
Karin Reijmar, Katarina Edwards, Karl Andersson, Víctor Agmo Hernández
Recent studies have identified PEG-stabilized lipid nanodisks (lipodisks) as promising carriers for cationic amphiphilic peptides with antimicrobial and anticancer activity. Using fluorimetric and nanogravimetric methods, we have in this work characterized the parameters describing and controlling the binding of three selected peptides (melittin, LL37, and magainin 2) onto lipodisks. It was found that the affinity of melittin for lipodisks is independent of the disk size and rim charge. On the other hand, the number of binding sites is strongly dependent on both parameters, with the highest loading being obtained for small disks with a negatively charged rim...
November 22, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27772956/effect-of-melittin-treatment-in-a-mouse-model-of-xenobiotic-induced-cholangitis-and-biliary-fibrosis
#13
Hyun-Jung Sung, Kyung-Hyun Kim, Young-In Maeng, Kwan-Kyu Park
No abstract text is available yet for this article.
February 2016: Pathology
https://www.readbyqxmd.com/read/27754384/metabolomic-profiling-of-the-effects-of-melittin-on-cisplatin-resistant-and-cisplatin-sensitive-ovarian-cancer-cells-using-mass-spectrometry-and-biolog-microarray-technology
#14
Sanad Alonezi, Jonans Tusiimire, Jennifer Wallace, Mark J Dufton, John A Parkinson, Louise C Young, Carol J Clements, Jin Kyu Park, Jong Woon Jeon, Valerie A Ferro, David G Watson
In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists...
October 13, 2016: Metabolites
https://www.readbyqxmd.com/read/27732908/when-and-how-the-melittin-ion-channel-exhibits-ohmic-behavior
#15
Lucia Becucci, Giovanni Aloisi, Rolando Guidelli
Melittin exhibits an ohmic behavior in a lipid bilayer having a DOPC distal leaflet and interposed between a 2.25nm tetraethyleneoxy chain tethered to a mercury drop and an aqueous solution. This behavior is induced in a pH6.8 buffer solution of 0.8μg/mL melittin by a pretreatment consisting of series of electrochemical impedance spectroscopy measurements at bias potentials varied by 50mV steps over a transmembrane potential range from about +250 to -250mV. This metastable ohmic behavior remains unchanged for hours, even after acidifying the solution to pH3...
February 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/27718471/pyrazole-derived-ultra-short-antimicrobial-peptidomimetics-with-potent-anti-biofilm-activity
#16
Mija Ahn, Pethaiah Gunasekaran, Ganesan Rajasekaran, Eun Young Kim, Soo-Jae Lee, Geul Bang, Kun Cho, Jae-Kyung Hyun, Hyun-Ju Lee, Young Ho Jeon, Nam-Hyung Kim, Eun Kyoung Ryu, Song Yub Shin, Jeong Kyu Bang
In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27693786/melittin-ameliorates-cvb3-induced-myocarditis-via-activation-of-the-hdac2-mediated-gsk-3%C3%AE-nrf2-are-signaling-pathway
#17
Tuanjie Wang, Jian Zhang, Aiju Xiao, Weiqing Liu, Yun Shang, Jindou An
Viral myocarditis (VMC) is characterized as an inflammatory process of the myocardium and can be fatal in infants and children. Melittin is a major polypeptide in honey bee venom that has been traditionally used against inflammation. However, its effect on VMC and the underlying molecular mechanism has not been reported. In this study, BALB/c mice were intraperitoneally injected with CVB3 to build a VMC model and treated with melittin. The results showed that melittin increased the mice's body weight and inhibited CVB3 replication...
September 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27677623/application-of-bee-venom-and-its-main-constituent-melittin-for-cancer-treatment
#18
Cui-Cui Liu, Ding-Jun Hao, Qian Zhang, Jing An, Jing-Jing Zhao, Bo Chen, Ling-Ling Zhang, Hao Yang
Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles...
September 27, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27666985/one-step-purification-of-melittin-derived-from-apis-mellifera-bee-venom
#19
Angela Ching Ling Teoh, Kyoung-Hwa Ryu, Eun Gyo Lee
The concern of the use of melittin in honey bee venom due to its adverse reaction caused by allergens such as phospholipase A2 (PLA₂) and hyaluronidase (HYA) has been an obstacle towards its usage. We developed a novel single-step method for melittin purification and the removal of PLA₂ and HYA. This study explores the influence of pH, buffer compositions, salt concentration and types of cation-exchange chromatography resins on the recovery of melittin and the removal of both HYA and PLA₂. Melittin can be readily purified with a strong cation-exchange resin at pH 6...
September 23, 2016: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27651455/phosphorylation-specific-status-of-rnai-triggers-in-pharmacokinetic-and-biodistribution-analyses
#20
Vladimir S Trubetskoy, Jacob B Griffin, Anthony L Nicholas, Eric M Nord, Zhao Xu, Ryan M Peterson, Christine I Wooddell, David B Rozema, Darren H Wakefield, David L Lewis, Steven B Kanner
The RNA interference (RNAi)-based therapeutic ARC-520 for chronic hepatitis B virus (HBV) infection consists of a melittin-derived peptide conjugated to N-acetylgalactosamine for hepatocyte targeting and endosomal escape, and cholesterol-conjugated RNAi triggers, which together result in HBV gene silencing. To characterize the kinetics of RNAi trigger delivery and 5'-phosphorylation of guide strands correlating with gene knockdown, we employed a peptide-nucleic acid (PNA) hybridization assay. A fluorescent sense strand PNA probe binding to RNAi duplex guide strands was coupled with anion exchange high performance liquid chromatography to quantitate guide strands and metabolites...
September 19, 2016: Nucleic Acids Research
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