• Title/Summary/Keyword: Cell selectivity

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Structure-Activity Relationships of Peptide Antibiotics with Improved Bacterial Cell Selectivity of Pseudin

  • Lee, Yeongjoon;Jeon, Dasom;Kim, Jin-Kyoung;Kim, Yangmee
    • Journal of the Korean Magnetic Resonance Society
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    • v.21 no.3
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    • pp.78-84
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    • 2017
  • Pseudin is a naturally occurring 24 amino-acid-residue antimicrobial peptide derived from the skin of paradoxical frog Pseud's paradoxa. It shows potency against the bacteria and antibiotic-resistant bacteria strain, but has high cytotoxicity against mammalian cell. In our previous study, substitution of $Pro^{11}$ for Gly (Ps-P) increased bacterial cell selectivity but decreased the antibacterial activity of pseudin. In this study, we designed pseudin analogue, Ps-4K-P with increased cationicity up to +7 in Ps-P by substituting Glu14, Gln10, Gln24, and Leu18 with Lys. Ps-4K-P showed improved potent antibacterial activity with high bacterial cell selectivity. We determined the tertiary structure of Ps-4K-P in the presence of DPC micelles by NMR spectroscopy and it has a hinge structure at $Pro^{11}$ followed by three turn helices from $Pro^{11}$ to $Val^{23}$ at the C-terminus. Amphipathicity with increased cationicity as well as helix-hinge-helix structural motif provided by introduction of a Pro at position $Gly^{11}$ are the crucial factors which confer antibacterial activity with bacterial cell selectivity to Ps-4K-P.

Cell Selectivity of an Antimicrobial Peptide Melittin Diastereomer with D-amino Acid in the Leucine Zipper Sequence

  • Zhu, Wan Long;Nan, Yong Hai;Hahm, Kyung-Soo;Shin, Song-Yub
    • BMB Reports
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    • v.40 no.6
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    • pp.1090-1094
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    • 2007
  • Melittin (ME), a linear 26-residue non-cell-selective antimicrobial peptide, displays strong lytic activity against bacterial and human red blood cells. To design ME analogue with improved cell selectivity, we synthesized a melittin diastereomer (ME-D) with D-amino acid in the leucine zipper sequence (Leu-6, Lue-13 and Ile-20). Compared to ME, ME-D exhibited the same or 2-fold higher antibacterial activity but 8-fold less hemolytic activity. Circular dichroism analysis revealed that ME-D has much less $\alpha$-helical content in $\alpha$-helical content in the presence of zwitterionic EYPC/cholesterol (10 : 1, w/w) liposomes compared to negatively charged EYPE/EYPG (7 : 3, w/w) liposomes. The blue shift of the fluorescence emission maximum of ME-D in zwitterionic EYPC/cholesterol (10 : 1, w/w) liposomes was much smaller than in negatively charged EYPE/EYPG (7 : 3, w/w) liposomes. These results suggested that the improvement in therapeutic index/cell selectivity of ME-D is correlated with its less permeability to zwitterionic membranes.

Structure and Bacterial Cell Selectivity of a Fish-Derived Antimicrobial Peptide, Pleurocidin

  • Yang Ji-Young;Shin Song-Yub;Lim Shin-Saeng;Hahm Kyung-Soo;Kim Yang-Mee
    • Journal of Microbiology and Biotechnology
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    • v.16 no.6
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    • pp.880-888
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    • 2006
  • Pleurocidin, an $\alpha$-helical cationic antimicrobial peptide, was isolated from skin mucosa of winter flounder (Pleuronectes americamus). It had strong antimicrobial activities against Gram-positive and Gram-negative bacteria, but had very weak hemolytic activity. The Gly$^{13,17}\rightarrow$Ala analog (pleurocidin-AA) showed similar antibacterial activities, but had dramatically increased hemolytic activity. The bacterial cell selectivity of pleurocidin was confirmed through the membrane-disrupting and membrane-binding affinities using dye leakage, tryptophan fluorescence blue shift, and tryptophan quenching experiments. However, the non-cell-selective antimicrobial peptide, pleurocidin-AA, interacts strongly with both negatively charged and zwitterionic phospholipid membranes, the latter of which are the major constituents of the outer leaflet of erythrocytes. Circular dihroism spectra showed that pleurocidin-AA has much higher contents of $\alpha$-helical conformation than pleurocidin. The tertiary structure determined by NMR spectroscopy showed that pleurocidin has a flexible. structure between the long helix from $Gly^3$ to $Gly^{17}$ and the short helix from $Gly^{17}$ to $Leu^{25}$. Cell-selective antimicrobial peptide pleurocidin interacts strongly with negatively charged phospholipid membranes, which mimic bacterial membranes. Structural flexibility between the two helices may play a key role in bacterial cell selectivity of pleurocidin.

Dynamic Channel Allocation Algorithm for Co-channel Interference Avoidance in Multi-cell OFDMA Systems (OFDMA 다중 셀 환경에서 동일 채널 간섭을 피하기 위한 동적 자원 할당 알고리즘)

  • Lee, Je-Min;Seo, Woo-Hyun;Wang, Hano;Hong, Dae-Sik
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.44 no.5
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    • pp.92-98
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    • 2007
  • We propose the schemes for the dynamic channel allocation (DCA) in multi-cell OFDMA systems to avoid co-channel interference (CCI) without the additional complexity. The allocatable subcarriers areas, which is designed to avoid CCI among cells, are determined for each cell. Each cell allocates the subcarriers within the allocatable subcarriers area of the cell independently. We consider the trade off between the reduced frequency selection diversity and the amount of CCI on a subcarrier by the determination of allocatable subcarriers area. Hence, the equal allocation bound scheme for the high selectivity channel and the flexible allocation bound scheme for the low selectivity channel are proposed. Through the numerical results, it is confirmed that the proposed schemes have better performance in the aspects of the number of overlapping allocated subcarriers, the capacity and the outage probability compared to the case which does not determined the allocatable subcarriers area.

Characterization of Commercial Membranes for Non-aqueous Vanadium Redox Flow Battery (비수계 바나듐 레독스 흐름 전지를 위한 상용 멤브레인의 특성분석)

  • Sung, Ki-Won;Shin, Sung-Hee;Moon, Seung-Hyeon
    • Korean Chemical Engineering Research
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    • v.51 no.5
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    • pp.615-621
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    • 2013
  • Membrane characterization methods for aqueous redox flow batteries aqueous RFBs were modified for non-aqueous RFBs. The modified characterization methods, such as ion exchange capacity, transport number, permeability and single cell test, were carried out to evaluate commercial membranes in non-aqueous electrolyte. It was found that columbic efficiency and energy efficiency in a single cell test were dependent on the ion selectivity of commercial anion exchange membranes. Neosepta AHA anion exchange membrane showed the anion transport number of 0.81, which is a relatively low ion selectivity in non-aqueous electrolyte, however, exhibited 92% of coulombic efficiency and 86% of energy efficiency in a single cell test. It was also found that a porous membrane without ion selectivity is suitable for a non-aqueous redox flow battery at a high current density.

Effect of Double Replacement of L-Pro, D-Pro, D-Leu or Nleu in Hydrophobic Face of Amphipathic α-Helical Model Antimicrobial Peptide on Structure, Cell Selectivity and Mechanism of Action

  • Shin, Song Yub
    • Bulletin of the Korean Chemical Society
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    • v.35 no.11
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    • pp.3267-3274
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    • 2014
  • In order to investigate the effects of the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu (the peptoid residue for Leu) in the hydrophobic face (positions 9 and 13) of amphipathic ${\alpha}$-helical non-cell-selective antimicrobial peptide $L_8K_9W_1$ on the structure, cell selectivity and mechanism of action, we synthesized a series of $L_8K_9W_1$ analogs with double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu in the hydrophobic face of $L_8K_9W_1$. In this study, we have confirmed that the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, or Nleu in the hydrophobic face of $L_8K_9W_1$ let to a great increase in the selectivity toward bacterial cells and a complete destruction of ${\alpha}$-helical structure. Interestingly, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu preferentially interacted with negatively charged phospholipids, but unlike $L_8K_9W_1$ and $L_8K_9W_1$-$\small{D}$-Leu, they did not disrupt the integrity of lipid bilayers and depolarize the bacterial cytoplasmic membrane. These results suggested that the mode of action of $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu involves the intracellular target other than the bacterial membrane. In particular, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu had powerful antimicrobial activity (MIC range, 1 to $4{\mu}M$) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Taken together, our results suggested that $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu with great cell selectivity may be promising candidates for novel therapeutic agents, complementing conventional antibiotic therapies to combat pathogenic microorganisms.

Cathode Catalyst of Direct Borohydride/Hydrogen Peroxide Fuel Cell for Space Exploration (우주탐사용 직접 수소화붕소나트륨/과산화수소 연료전지의 환원극 촉매)

  • YU, SU SANG;OH, TAEK HYUN
    • Journal of Hydrogen and New Energy
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    • v.31 no.5
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    • pp.444-452
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    • 2020
  • This study investigated the cathode catalyst of direct borohydride/hydrogen peroxide fuel cells for space exploration. Various catalysts such as Au, Ag, and Ni were supported on multiwalled carbon nanotubes (MWCNTs). Various techniques, such as transmission electron microscopy, Brunauer-Emmett-Teller method, scanning electron microscopy, and X-ray diffraction were conducted to investigate the characteristics of the catalysts. Fuel cell tests were performed to evaluate the performance of the catalysts. Ag/MWCNTs exhibited better catalytic activity than the Ni/MWCNTs and better catalytic selectivity of the Au/MWCNTs. Ag/MWCNTs presented good catalytic activity and selectivity even at an elevated operating temperature. The performance of Ag/MWCNTs was also stable for up to 60 minutes.

Design of Short Indolicidin Analogs with Enhanced Prokaryotic Selectivity (증가된 원핵세포선택성을 가진 짧은 인돌리시딘 유사체의 설계)

  • Shin, Song Yub
    • Microbiology and Biotechnology Letters
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    • v.40 no.4
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    • pp.409-413
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    • 2012
  • Indolicidin (ID) is a 13-residue Trp-rich antimicrobial peptide (AMP) isolated from bovine neutrophils. In addition to having a high antimicrobial potency, it is also toxic to mammalian cells. To develop novel ID-derived AMPs with shorter lengths and enhanced prokaryotic selectivities (meaning potent antimicrobial activity against bacterial cells without toxicity against mammalian cells) over the parental ID, several ID analogs were designed and synthesized. Finally, 10-residue ID analogs (SI, SI-PA, SI-WF and SI-WL) with much higher prokaryotic selectivity than the parental ID were developed. Our results suggest that the hydrophobic and aromatic amino acids at the central position of the analog SI with the highest prokaryotic selectivity are important for potent antimicrobial activity, but two Pro residues do not affect antimicrobial activity. The order of prokaryotic selectivity for ID and its designed analogs was SI > SI-PA > SI-WF > SI-WL > ID > SI-WA. Taken together, our designed short ID analogs could be developed as therapeutic agents for treating bacterial infections.

Descriptor-Based Profile Analysis of Kinase Inhibitors to Predict Inhibitory Activity and to Grasp Kinase Selectivity

  • Park, Hyejin;Kim, Kyeung Kyu;Kim, ChangHoon;Shin, Jae-Min;No, Kyoung Tai
    • Bulletin of the Korean Chemical Society
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    • v.34 no.9
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    • pp.2680-2684
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    • 2013
  • Protein kinases (PKs) are an important source of drug targets, especially in oncology. With 500 or more kinases in the human genome and only few kinase inhibitors approved, kinase inhibitor discovery is becoming more and more valuable. Because the discovery of kinase inhibitors with an increased selectivity is an important therapeutic concept, many researchers have been trying to address this issue with various methodologies. Although many attempts to predict the activity and selectivity of kinase inhibitors have been made, the issue of selectivity has not yet been resolved. Here, we studied kinase selectivity by generating predictive models and analyzing their descriptors by using kinase-profiling data. The 5-fold cross-validation accuracies for the 51 models were between 72.4% and 93.7% and the ROC values for all the 51 models were over 0.7. The phylogenetic tree based on the descriptor distance is quite different from that generated on the basis of sequence alignment.