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131.
Galina M. Zats Marina Kovaliov Amnon Albeck Shimon Shatzmiller 《Journal of peptide science》2015,21(6):512-519
Antimicrobial peptides (AMPs) appear to be good candidates for the development of new antibiotic drugs. We describe here the synthesis of peptidomimetic compounds that are based on a benzodiazepine scaffold flanked with positively charged and hydrophobic amino acids. These compounds mimic the essential properties of cationic AMPs. The new design possesses the benzodiazepine scaffold that is comprised of two glycine amino acids and which confers flexibility and aromatic hydrophobic ‘back’, and two arms used for further synthesis on solid phase for incorporation of charged and hydrophobic amino acids. This approach allowed us a better understanding of the influence of these features on the antimicrobial activity and selectivity. A novel compound was discovered which has MICs of 12.5 µg/ml against Staphylococcus aureus and 25 µg/ml against Escherichia coli, similar to the well‐known antimicrobial peptide MSI‐78. In contrast to MSI‐78, the above mentioned compound has lower lytic effect against mammalian red blood cells. These peptidomimetic compounds will pave the way for future design of potent synthetic mimics of AMPs for therapeutic and biomedical applications. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
132.
Pavel V. Panteleev Ilia A. Bolosov Sergey V. Balandin Tatiana V. Ovchinnikova 《Journal of peptide science》2015,21(2):105-113
β‐Hairpin antimicrobial peptides are among the most potent peptide antibiotics of animal origin. Arenicins, isolated earlier from marine polychaeta lugworm Arenicola marina, belong to a family of β‐hairpin antimicrobial peptides and display a broad spectrum of biological activities. However, despite being potent antimicrobials, arenicins are partially unapplicable as therapeutics as a result of their relatively high cytotoxicity against mammalian cells. In this study, a template‐based approach was used to create therapeutically valuable analogs of arenicin‐1 and identify amino acid residues important for antibacterial and cytotoxic activities of the peptide. The plasmids encoding recombinant analogs were constructed by mutagenesis technique based on inverse PCR amplification of the whole arenicin‐1 expression plasmid. The analogs were produced as a part of the fusion proteins in Escherichia coli. It was shown that an obvious reduction in hemolytic activity without lose of antimicrobial activity can be achieved by a single amino acid substitution in the non‐polar face of the molecule with hydrophilic residues such as serine and arginine. As the result, the selective analog with 50‐fold improved therapeutic index was developed. The circular dichroism spectra demonstrated that the secondary structure of the analog was similar to the natural arenicin‐1 in water solution and sodium dodecyl sulfate micelles but significantly differed in the presence of dodecylphosphocholine micelles mimicking mammalian membranes. Similarly to arenicin‐1, the designed analog killed bacteria via induction of the membrane damage, assessed using the fluorescent dye SYTOX Green uptake. Our results afford molecular insight into mechanism of antimicrobial action of the designed arenicin analogs and their possible clinical application. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
133.
Lipid‐dependent pore formation by antimicrobial peptides arenicin‐2 and melittin demonstrated by their proton transfer activity
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Sergei V. Sychev Sergey V. Balandin Pavel V. Panteleev Leonid I. Barsukov Tatiana V. Ovchinnikova 《Journal of peptide science》2015,21(2):71-76
This work presents a comparative study of proton transfer activity (PTA) of two cationic (+6) antimicrobial peptides, β‐structural arenicin‐2 and α‐helical melittin. A new approach was proposed for the detection of passive proton transfer by using proteoliposomes containing bacteriorhodopsin, which creates a small light‐induced electrochemical proton gradient ?ΔpH. Addition of several nanomoles of the peptides lowers ?ΔpH that is proximately indicative of the pore formation. The quantitative analysis of sigmoidal dependences of ?pH on the peptides concentration was carried out using liposomes prepared from PC, PC/PE, PC/PE/PI and PC/PG. Substitution of PC‐containing liposomes with PE‐containing ones, having negative spontaneous curvature, reduced the PTA of α‐helical melittin and increased that of β‐structural arenicin‐2. This result indicates an essential difference in the pore formation by these peptides. Further increase of PTA in response to arenicin‐2 (in contrast to melittin) was observed in the liposomes prepared from PC/PE/PI. The data analysis leads to the conclusion that PTA is influenced by (i) efficiency of the pore assemblage, which depends on the structure of pore‐forming peptides, and the spontaneous curvature of lipids and (ii) the presence of mobile protons in the polar head groups of phospholipids. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
134.
Alexey Teplyakov Galina Obmolova Gabriela Canziani Yonghong Zhao Lester Gutshall Sonia S. Jung Gary L. Gilliland 《Journal of molecular recognition : JMR》2011,24(4):570-575
Alzheimer's disease is a progressive neurodegenerative disease characterized by extracellular deposits of β‐amyloid (Aβ) plaques. Aggregation of the Aβ42 peptide leading to plaque formation is believed to play a central role in Alzheimer's disease pathogenesis. Anti‐Aβ monoclonal antibodies can reduce amyloid plaques and could possibly be used for immunotherapy. We have developed a monoclonal antibody C706, which recognizes the human Aβ peptide. Here we report the crystal structure of the antibody Fab fragment at 1.7 Å resolution. The structure was determined in two crystal forms, P21 and C2. Although the Fab was crystallized in the presence of Aβ16, no peptide was observed in the crystals. The antigen‐binding site is blocked by the hexahistidine tag of another Fab molecule in both crystal forms. The poly‐His peptide in an extended conformation occupies a crevice between the light and heavy chains of the variable domain. Two consecutive histidines (His4–His5) stack against tryptophan residues in the central pocket of the antigen‐binding surface. In addition, they form hydrogen bonds to the acidic residues at the bottom of the pocket. The mode of his‐tag binding by C706 resembles the Aβ recognition by antibodies PFA1 and WO2. All three antibodies recognize the same immunodominant B‐cell epitope of Aβ. By similarity, residues Phe–Arg–His of Aβ would be a major portion of the C706 epitope. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
135.
miRTour: Plant miRNA and target prediction tool 总被引:1,自引:0,他引:1
MicroRNAs (miRNAs) are important negative regulators of gene expression in plant and animals, which are endogenously produced from their own genes. Computational comparative approach based on evolutionary conservation of mature miRNAs has revealed a number of orthologs of known miRNAs in different plant species. The homology-based plant miRNA discovery, followed by target prediction, comprises several steps, which have been done so far manually. Here, we present the bioinformatics pipeline miRTour which automates all the steps of miRNA similarity search, miRNA precursor selection, target prediction and annotation, each of them performed with the same set of input sequences. AVAILABILITY: The database is available for free at http://bio2server.bioinfo.uni-plovdiv.bg/miRTour/ 相似文献
136.
Khomyakova EA Zubin EM Smirnov IP Pozmogova GE Stetsenko DA Oretskaya TS 《Nucleosides, nucleotides & nucleic acids》2011,30(7-8):577-584
An efficient method for the synthesis of DNA or RNA oligonucleotide 2'-hydrazides is described. Fully deprotected oligonucleotides containing a hydrazide group at the 2'-position of a uridine residue were obtained by a novel two-step procedure: periodate cleavage of an oligonucleotide with 1,2-diol group followed by conversion of the aldehyde to hydrazide with an extended linker arm using a homobifunctional reagent succinic dihydrazide and NaBH(3)CN. The resulting oligonucleotide 2'-hydrazides were efficiently conjugated by a click-type reaction at acidic pH to aliphatic or aromatic aldehydes with or without NaBH(3)CN reduction to afford novel 2'-conjugates. 相似文献
137.
Nazaret Hidalgo Giulia Mangiameli Teresa Manzano Galina G. Zhadan John F. Kennedy Valery L. Shnyrov Manuel G. Roig 《Biotechnology and Bioprocess Engineering》2011,16(4):821-829
The degradation and removal of a series of dyes used in the textile industry for polyester/wool (PES/WO) blends and present
in effluents, such as Green, Ash-Grey, Black, Navy Blue, Red and Yellow Domalan, and Orange and Red Bemacid, by catalytic
action, in the presence of H2O2, of extracts of a novel peroxidase from postharvest lentil stubble was investigated. The extracts of this peroxidase (LSP)
were effective in degrading these lastgeneration textile dyes, especially Green Domalan, Orange Bemacid, Grey and Black Domalan.
A sensitivity study was carried out for Green Domalan biodegradation to determine the effects of process parameters such as
pH, H2O2, enzyme and dye concentrations, contact and centrifugation times, and temperature. Standard ecotoxicity studies performed
with Vibrio fischeri revealed that the dye solutions treated with peroxidase and H2O2 were less ecotoxic than the untreated ones. 相似文献
138.
Chertkov O Brown PJ Kysela DT de Pedro MA Lucas S Copeland A Lapidus A Del Rio TG Tice H Bruce D Goodwin L Pitluck S Detter JC Han C Larimer F Chang YJ Jeffries CD Land M Hauser L Kyrpides NC Ivanova N Ovchinnikova G Tindall BJ Göker M Klenk HP Brun YV 《Standards in genomic sciences》2011,5(3):287-297
The family Hyphomonadaceae within the Alphaproteobacteria is largely comprised of bacteria isolated from marine environments with striking morphologies and an unusual mode of cell growth. Here, we report the complete genome sequence Hirschia baltica, which is only the second a member of the Hyphomonadaceae with a published genome sequence. H. baltica is of special interest because it has a dimorphic life cycle and is a stalked, budding bacterium. The 3,455,622 bp long chromosome and 84,492 bp plasmid with a total of 3,222 protein-coding and 44 RNA genes were sequenced as part of the DOE Joint Genome Institute Program CSP 2008. 相似文献
139.
Chertkov O Sikorski J Nolan M Lapidus A Lucas S Del Rio TG Tice H Cheng JF Goodwin L Pitluck S Liolios K Ivanova N Mavromatis K Mikhailova N Ovchinnikova G Pati A Chen A Palaniappan K Djao OD Land M Hauser L Chang YJ Jeffries CD Brettin T Han C Detter JC Rohde M Göker M Woyke T Bristow J Eisen JA Markowitz V Hugenholtz P Klenk HP Kyrpides NC 《Standards in genomic sciences》2011,4(1):13-22
Thermomonospora curvata Henssen 1957 is the type species of the genus Thermomonospora. This genus is of interest because members of this clade are sources of new antibiotics, enzymes, and products with pharmacological activity. In addition, members of this genus participate in the active degradation of cellulose. This is the first complete genome sequence of a member of the family Thermomonosporaceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 5,639,016 bp long genome with its 4,985 protein-coding and 76 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
140.
Zeytun A Sikorski J Nolan M Lapidus A Lucas S Han J Tice H Cheng JF Tapia R Goodwin L Pitluck S Liolios K Ivanova N Mavromatis K Mikhailova N Ovchinnikova G Pati A Chen A Palaniappan K Ngatchou-Djao OD Land M Hauser L Jeffries CD Han C Detter JC Ubler S Rohde M Tindall BJ Göker M Wirth R Woyke T Bristow J Eisen JA Markowitz V Hugenholtz P Klenk HP Kyrpides NC 《Standards in genomic sciences》2011,4(2):131-143
Hydrogenobacter thermophilus Kawasumi et al. 1984 is the type species of the genus Hydrogenobacter. H. thermophilus was the first obligate autotrophic organism reported among aerobic hydrogen-oxidizing bacteria. Strain TK-6(T) is of interest because of the unusually efficient hydrogen-oxidizing ability of this strain, which results in a faster generation time compared to other autotrophs. It is also able to grow anaerobically using nitrate as an electron acceptor when molecular hydrogen is used as the energy source, and able to aerobically fix CO(2)via the reductive tricarboxylic acid cycle. This is the fifth completed genome sequence in the family Aquificaceae, and the second genome sequence determined from a strain derived from the original isolate. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 1,742,932 bp long genome with its 1,899 protein-coding and 49 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献