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Michael E Selsted - One of the best experts on this subject based on the ideXlab platform.
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Anti-HIV-1 activity of Indolicidin, an antimicrobial peptide from neutrophils
2013Co-Authors: Edward W. Robinson, B Mcdougall, Dat Tran, Michael E SelstedAbstract:Abstract: Indolicidin is a tridecapeptide amide isolated from the cytoplasmic granules of bovine neutrophils. It has potent, broad spectrum microbicidal activities in vitro that are thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that Indolicidin would be active against HIV-1, an enveloped virus. Indolicidin was reproducibly virucidal against HIV-1 at a concentration of 333 �g/mL (174 �M) with a 50 % inhibitory dose between 67 and 100 �g/mL. At 37°C, killing was rapid with G50 % killing of HIV occurring within 5 min, and nearly 100 % viral inactivation achieved by 60 min. The anti-HIV activity of Indolicidin was temperature-sensitive, a finding consistent with a membrane-mediated antiviral mechanism. Parallel experiments revealed that Indolicidin lysed cultured lymphoblastoid cells at concentrations similar to those required for antiviral activity. However, a des-R13-amide Indolicidin analog (R12-OH), previously shown to have less antibacterial activity than Indolicidin, was significantly less active against HIV and was non-toxic to lymphoid target cells at concentrations up to 333 �g/mL, the highest level tested. J
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synthesis and characterization of Indolicidin a tryptophan rich antimicrobial peptide from bovine neutrophils
International Journal of Peptide and Protein Research, 2009Co-Authors: Robert J Van Abel, Dat Tran, Yiquan Q Tang, V S V Rao, Craig H Dobbs, George Barany, Michael E SelstedAbstract:Indolicidin, a novel tryptophan-rich microbicidal tridecapeptide amide isolated originally from granules of bovine neutrophils, has been prepared by optimized manual and automated protocols of stepwise solid-phase synthesis with Nα-9-fluorenylmethyloxycarbonyl (Fmoc) amino acid derivatives. Both standard polystyrene (PS) and polyethylene glycol-polystyrene (PEG-PS) graft supports were used in combination with handles that provide C-terminal peptide amides: 5-(4-Fmoc-aminomethyl-3,5-dimethoxyphenoxy)valeric acid (PAL) or 5-(9-Fmoc-aminoxanthen-2-oxy)valeric acid (XAL). Final deprotection/cleavage was carried out with reagent K, trifluoroacetic acid–phenol–water–thioanisole–1,2-ethanedithiol (82.5:5:5:5:2.5), or reagent B, trifluoroacetic acid–phenol–water–tri(isopropyl)silane (88:5:5:2), and related cocktails. Initial purities as high as 93% were obtained immediately following cleavage. In the largest-scale synthesis carried out, 0.8 g of HPLC-purified Indolicidin (> 99% pure) was obtained, representing a 39% overall yield based on C-terminal Arg(Pmc) anchored to PAL-PS-resin. The main synthetic product, and some by-products, were characterized by analytical high-performance liquid chromatography (HPLC), sequencing, and fast atom bombardment mass spectrometry (FABMS). The antimicrobial potencies of natural and synthetic Indolicidin, as determined by in vitro antibacterial and antifungal assays, were identical. Further, the reactivities of natural and synthetic peptides with anti-Indolicidin antibody were indistinguishable. © Munksgaard 1995.
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formation and characterization of a single trp trp cross link in Indolicidin that confers protease stability without altering antimicrobial activity
Journal of Biological Chemistry, 2000Co-Authors: Klara Osapay, Alexey S Ladokhin, Stephen H White, Dat Tran, Agnes Henschen, Michael E SelstedAbstract:Indolicidin is a 13-residue cationic, antimicrobial peptide-amide isolated from the cytoplasmic granules of bovine neutrophils. The unique composition of Indolicidin distinguishes it from alpha-helical and beta-structured cationic peptides, because five of Indolicidin's 13 residues are tryptophans: H-Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH(2). Solid phase synthesis of Indolicidin gave rise to a minor byproduct that possessed unusual fluorescence and UV absorbance properties compared with authentic Indolicidin. The byproduct was purified by combined ion exchange and reversed phase high pressure liquid chromatography steps and was shown be identical to authentic Indolicidin in its microbicidal activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and Cryptococcus neoformans. Mass analysis of the byproduct revealed a 2-atomic mass unit reduction compared with Indolicidin, suggesting the deprotonation of two indole side chains to form an intrachain delta(1),delta(1)'-ditryptophan derivative. We confirmed the nature of the cross-linked byproduct, termed X-Indolicidin, by absorbance and fluorescence spectroscopy, peptide mapping, and sequence analysis. Edman degradation revealed that Trp-6 and Trp-9 were covalently cross-linked. Compared with Indolicidin, X-Indolicidin was partially resistant to digestion with trypsin and chymotrypsin, suggesting that the ditryptophan stabilizes a subset of molecular conformations that are protease resistant but that are absent in the native structure.
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cd spectra of Indolicidin antimicrobial peptides suggest turns not polyproline helix
Biochemistry, 1999Co-Authors: Alexey S Ladokhin, Michael E Selsted, Stephen H WhiteAbstract:Indolicidin is a 13-residue antimicrobial peptide-amide isolated from the cytoplasmic granules of bovine neutrophils that contains five Trp and three Pro residues. Falla et al. [(1996) J. Biol. Chem. 271, 19298] suggested that Indolicidin forms a poly-l-proline II helix based upon the circular dichroism (CD) spectra of a closely related peptide (Indolicidin methyl ester). In contrast, we found no evidence of poly-l-proline II helix formation in the CD spectra of native Indolicidin in various solvents or when bound to micelles and membranes [Ladokhin et al. (1997) Biophys. J. 72, 794]. We interpreted the spectra as arising from unordered and/or β-turn structures, but noted a sharp negative band at 227 nm arising from the tryptophan residues that would mask spectral features characteristic of poly-l-proline II helix. We have reexamined this issue by means of CD measurements of native Indolicidin and several of its analogues. None of the features characteristic of a poly-l-proline helix (or α- or 310-helix) ...
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anti hiv 1 activity of Indolicidin an antimicrobial peptide from neutrophils
Journal of Leukocyte Biology, 1998Co-Authors: W E Robinson, Dat Tran, B Mcdougall, Michael E SelstedAbstract:Indolicidin is a tridecapeptide amide isolated from the cytoplasmic granules of bovine neutrophils. It has potent, broad spectrum microbicidal activities in vitro that are thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that Indolicidin would be active against HIV-1, an enveloped virus. Indolicidin was reproducibly virucidal against HIV-1 at a concentration of 333 microg/mL (174 microM) with a 50% inhibitory dose between 67 and 100 microg/mL. At 37 degrees C, killing was rapid with >50% killing of HIV occurring within 5 min, and nearly 100% viral inactivation achieved by 60 min. The anti-HIV activity of Indolicidin was temperature-sensitive, a finding consistent with a membrane-mediated antiviral mechanism. Parallel experiments revealed that Indolicidin lysed cultured lymphoblastoid cells at concentrations similar to those required for antiviral activity. However, a des-R13-amide Indolicidin analog (R12-OH), previously shown to have less antibacterial activity than Indolicidin, was significantly less active against HIV and was non-toxic to lymphoid target cells at concentrations up to 333 microg/mL, the highest level tested.
Emilia Galdiero - One of the best experts on this subject based on the ideXlab platform.
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efficiency of gold nanoparticles coated with the antimicrobial peptide Indolicidin against biofilm formation and development of candida spp clinical isolates
Infection and Drug Resistance, 2018Co-Authors: Elisabetta De Alteriis, Annarita Falanga, Stefania Galdiero, Marco Guida, Valeria Maselli, Federica Maria Di Lella, Renato Gesuele, Emilia GaldieroAbstract:Background This article examines the use of a novel nano-system, gold nanoparticles coated with Indolicidin (AuNPs-Indolicidin), against pathogenic Candida albicans biofilms. Candida species cause frequent infections owing to their ability to form biofilms, primarily on implant devices. Materials and methods We used an integrated approach, evaluating the effect of AuNPs-Indolicidin on prevention and eradication of Candida biofilms formed in multi-well polystyrene plates, with relative gene expression assays. Four biofilm-associated genes (FG1, HWP1, ALS1 and ALS3, and CDR1 and CDR2) involved in efflux pump were analyzed using reverse transcription polymerase chain reaction. Results Treatment with the nano-complex significantly inhibits the capacity of C. albicans to form biofilms and impairs preformed mature biofilms. Treatment with AuNPs-Indolicidin results in an increase in the kinetics of Rhodamine 6G efflux and a reduction in the expression of biofilm-related genes. Conclusion These data provide a chance to develop novel therapies against nosocomially acquired refractory C. albicans biofilms.
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metabolomic and oxidative effects of quantum dots Indolicidin on three generations of daphnia magna
Aquatic Toxicology, 2018Co-Authors: Annarita Falanga, Stefania Galdiero, Marco Guida, Flavia Anna Mercurio, Antonietta Siciliano, Lucia Lombardi, Giovanni Libralato, Marilisa Leone, Emilia GaldieroAbstract:This study evaluated the effect of QDs functionalized with the antimicrobial peptide Indolicidin on oxidative stress and metabolomics profiles of Daphnia magna across three generations (F0, F1, and F2). Exposing D. magna to sub-lethal concentrations of the complex QDs-Indolicidin, a normal survival of daphnids was observed from F0 to F2, but a delay of first brood, fewer broods per female, a decrease of length of about 50% compared to control. In addition, QDs-Indolicidin induced a significantly higher production of reactive oxygen species (ROS) gradually in each generation and an impairment of enzymes response to oxidative stress such as superoxide dismutase (SOD), catalase (CAT) and glutathione transferase (GST). Effects were confirmed by metabolomics profiles that pointed out a gradual decrease of metabolomics content over the three generations and a toxic effect of QDs-Indolicidin likely related to the higher accumulation of ROS and decreased antioxidant capacity in F1 and F2 generations. Results highlighted the capability of metabolomics to reveal an early metabolic response to stress induced by environmental QDs-Indolicidin complex.
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genotoxicity of gold nanoparticles functionalized with Indolicidin towards saccharomyces cerevisiae
Journal of Environmental Sciences-china, 2017Co-Authors: Elisabetta De Alteriis, Annarita Falanga, Stefania Galdiero, Marco Guida, Valeria Maselli, Emilia GaldieroAbstract:The toxic effects of gold nanoparticles surface-functionalized with the antimicrobial peptide Indolicidin (AuNPs-Indolicidin) towards the yeast Saccharomyces cerevisiae, one of the major eukaryotic model organisms, have been evaluated. Growth and survival, genotoxicity, as measured by comet assay, and expression of the YCA1, an apoptosis indicating gene, following 72hr exposure of yeast to AuNPs-Indolicidin, and to AuNPs and Indolicidin alone have been examined. The gold nanoparticles exerted toxicity with DNA damage, accompanied by reactive oxygen species production (ROS), but they do not inhibit yeast growth and viability. Genotoxicity was less pronounced for surface-functionalized nanoparticles, showing that S. cerevisiae is quite resistant to the complex AuNPs-Indolicidin. A progressive reduction of the genotoxic effect was observed along 72hr exposure, presumably due to the activation of DNA repair mechanisms. These findings suggest the occurrence of a physiological protective response of S. cerevisiae towards nanoparticles, thereby providing useful information to the assessment of the environmental impact of metal nanoparticles.
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an integrated study on antimicrobial activity and ecotoxicity of quantum dots and quantum dots coated with the antimicrobial peptide Indolicidin
International Journal of Nanomedicine, 2016Co-Authors: Emilia Galdiero, Stefania Galdiero, Marco Guida, Valeria Maselli, Antonietta Siciliano, Lucia Lombardi, Renato Gesuele, Domenico Fulgione, Annarita FalangaAbstract:This study attempts to evaluate the antimicrobial activity and the ecotoxicity of quantum dots (QDs) alone and coated with Indolicidin. To meet this objective, we tested the level of antimicrobial activity on Gram-positive and Gram-negative bacteria, and we designed an ecotoxicological battery of test systems and indicators able to detect different effects using a variety of end points. The antibacterial activity was analyzed against Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 1025), Escherichia coli (ATCC 11229), and Klebsiella pneumoniae (ATCC 10031), and the results showed an improved germicidal action of QDs-Ind. Toxicity studies on Daphnia magna indicated a decrease in toxicity for QDs-Ind compared to QDs alone, lack of bioluminescence inhibition on Vibrio fisheri, and no mutations in Salmonella typhimurium TA 100. The comet assay and oxidative stress experiments performed on D. magna showed a genotoxic and an oxidative damage with a dose-response trend. Indolicidin retained its activity when bound to QDs. We observed an enhanced activity for QDs-Ind. The presence of Indolicidin on the surface of QDs was able to decrease its QDs toxicity.
Minghsi Huang - One of the best experts on this subject based on the ideXlab platform.
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mucosal delivery of a combination adjuvant comprising emulsified fine particles and ld Indolicidin enhances serological immunity to inactivated influenza virus
Microbes and Infection, 2016Co-Authors: Shihhsiung Dai, Minghsi Huang, Pele ChongAbstract:Here we investigate the immunogenicity of a combination adjuvant comprising emulsified fine particles (namely PELC) together with LD-Indolicidin, a peptiomimetic stereoisomer of the bovine neutrophil peptide Indolicidin. We demonstrated that intranasal vaccination with either PELC/LD-Indolicidin or Alum enhances protective influenza-specific serological immunity in mice; however, the adjuvant potency of Alum was rather reduced when the mice vaccinated orally with formulated influenza vaccines. The information gathered from this study will enhance our effort in the formulation design as well as the optimization of alternative administration routes for prophylactic vaccines against emerging infectious diseases, in particular pandemic influenza.
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Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG–PLA Conjugate for Tuning Immunity
2015Co-Authors: Fanny Coumes, Chiungyi Huang, Chung-hsiung Huang, Jean Coudane, Dominique Domurado, Vincent Darcos, Minghsi HuangAbstract:Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-Indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion. A peptide/polymer conjugate, named LD-Indolicidin–PEG-PLA, was synthesized by conjugation of the amine end-group of LD-Indolicidin to the N-hydroxysuccinimide-activated carboxyl end-group of PEG. As an adjuvant for cancer immunotherapeutic use, TAA vaccine candidate formulated with the LD-Indolicidin–PEG-PLA-stabilized squalene-in-water emulsion could effectively help to elicit a T helper (Th)1-dominant antigen-specific immune response as well as antitumor ability, using ovalbumin (OVA) protein/EG7 cells as a TAA/tumor cell model. Taken together, these results open up a new approach to the development of immunomodulatory antigen delivery systems for vaccine adjuvants and cancer immunotherapy technologies
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enzymatic stability and immunoregulatory efficacy of a synthetic Indolicidin analogue with regular enantiomeric sequence
ACS Medicinal Chemistry Letters, 2013Co-Authors: Chingyun Chang, Chihwei Lin, Shengkuo Chiang, Poling Chen, Chiungyi Huang, Shihjen Liu, Pele Chong, Minghsi HuangAbstract:Cell-mediated immunity plays a major role in protecting the host from viral infections and tumor challenge. Here, we report the enzymatic stability and adjuvanticity of a peptiomimetic stereoisomer of the bovine neutrophil peptide Indolicidin. The analogue, dubbed ld-Indolicidin, contains the regular enantiomeric sequence of Indolicidin and is synthesized by general stepwise solid-phase strategy. ld-Indolicidin possesses high resistance to enzymatic degradation and shows tolerance in mice. As vaccine adjuvant, ld-Indolicidin is better able than the native form of Indolicidin to enhance cell-mediated immune responses, using inactivated H5N1 virus as a model antigen. Taken together, these results open up a new approach to the development of vaccine adjuvants and immunotherapy technologies.
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Enzymatic Stability and Immunoregulatory Efficacy of a Synthetic Indolicidin Analogue with Regular Enantiomeric Sequence
2013Co-Authors: Chingyun Chang, Chihwei Lin, Shengkuo Chiang, Poling Chen, Chiungyi Huang, Shihjen Liu, Pele Chong, Minghsi HuangAbstract:Cell-mediated immunity plays a major role in protecting the host from viral infections and tumor challenge. Here, we report the enzymatic stability and adjuvanticity of a peptiomimetic stereoisomer of the bovine neutrophil peptide Indolicidin. The analogue, dubbed ld-Indolicidin, contains the regular enantiomeric sequence of Indolicidin and is synthesized by general stepwise solid-phase strategy. ld-Indolicidin possesses high resistance to enzymatic degradation and shows tolerance in mice. As vaccine adjuvant, ld-Indolicidin is better able than the native form of Indolicidin to enhance cell-mediated immune responses, using inactivated H5N1 virus as a model antigen. Taken together, these results open up a new approach to the development of vaccine adjuvants and immunotherapy technologies
Robert E. W. Hancock - One of the best experts on this subject based on the ideXlab platform.
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the novel adjuvant combination of cpg odn Indolicidin and polyphosphazene induces potent antibody and cell mediated immune responses in mice
Vaccine, 2009Co-Authors: Jennifer Kovacsnolan, Robert E. W. Hancock, Havard Jenssen, Laura Latimer, Abdolamir Landi, Lorne A Babiuk, S Van Drunen Littelvan Den HurkAbstract:The need to enhance the immunogenicity of purified subunit antigens and modulate resulting immune responses has prompted the development of new adjuvants. Here, the ability of CpG oligodeoxynucleotides (ODN), a bovine host defence peptide Indolicidin, and polyphosphazene to synergistically combine and enhance innate and adaptive immune responses was examined in mice. In vitro, the adjuvant combination of CpG ODN, Indolicidin and polyphosphazene (CpG/indol/PP) enhanced the secretion of TNF-, IL-12p40, and IL-6 by bone marrow-derived DCs (BMDCs) when compared to the individual components. When co-formulated with ovalbumin (OVA), CpG/indol/PP formed antigen-adjuvant complexes, and enhanced antibody and cell-mediated responses in mice, via both MHC I and II pathways, promoting a more balanced antibody-mediated and type 1-biased cell-mediated immune response. Furthermore, substitution of the proline residues of Indolicidin with arginine increased the synergistic adjuvant effect of the peptide, and induced significantly higher IgG1 and IgG2a titers and IFN- secretion, as well as increased uptake by antigen presenting cells. These results clearly demonstrate that the use of a combination of CpG ODN, Indolicidin, and polyphosphazene as adjuvant can significantly enhance an antigen-specific immune response.
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antiviral Indolicidin variant peptides evaluation for broad spectrum disease resistance in transgenic nicotiana tabacum
Plant Science, 2007Co-Authors: Apurva Bhargava, Robert E. W. Hancock, Milan Osusky, Benjamin S Forward, William W Kay, Santosh MisraAbstract:Cationic peptides play an important role in the natural defenses against microbial infections of most of the living organisms. Indolicidin, a cationic peptide derived from bovine neutrophils, demonstrates in vitro antibacterial, antifungal and antiviral activity against animal pathogens. To evaluate efficacy of this peptide aganist plant pathogens, especially viruses, here we describe engineering transgenic plants, expressing Indolicidin variants (10R and 11R). The variants were tested in vitro, for their effectiveness against plant pathogenic bacteria, fungi and TMV. Genes encoding these peptides were introduced into the tobacco cultivar (Nicotiana tabacum var. Xanthi). Leaf assays of transgenic plants showed enhanced resistance against several pathogens including significant resistance against TMV challenge. This is the first report of heterologous cationic peptide mediated antiviral resistance in engineered plants.
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structure based design of an Indolicidin peptide analogue with increased protease stability
Biochemistry, 2003Co-Authors: Annett Rozek, Carol L. Friedrich, Jonpaul S Powers, Robert E. W. HancockAbstract:Indolicidin is an antimicrobial cationic peptide with broad-spectrum activity isolated from bovine neutrophils. An Indolicidin analogue CP-11, ILKKWPWWPWRRK-NH2, with improved activity against Gram-negative bacteria had increased positive charge and amphipathicity while maintaining the short length of the parent molecule. The structure of CP-11 in the presence of dodecylphosphocholine (DPC) micelles was determined using nuclear magnetic resonance spectroscopy. CP-11 was found to be an amphipathic molecule with a U-shaped backbone bringing the N- and C-termini in close proximity. On the basis of this close proximity, a cyclic disulfide-bonded peptide cycloCP-11, ICLKKWPWWPWRRCK-NH2, was designed to stabilize the lipid-bound structure and to increase protease resistance. The three-dimensional structure of cycloCP-11 was determined under the same conditions as for the linear peptide and was found to be similar to CP-11. Both CP-11 and cycloCP-11 associated with phospholipid membranes in a similar manner as i...
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membrane binding and permeation by Indolicidin analogs studied by a biomimetic lipid polydiacetylene vesicle assay
Peptides, 2003Co-Authors: Revital Halevy, Robert E. W. Hancock, Annett Rozek, Sofiya Kolusheva, Raz JelinekAbstract:Membrane binding and relative penetration of Indolicidin analogs were studied using lipid/polydiacetylene (PDA) chromatic biomimetic membranes. Colorimetric and fluorescence analyses determined that an Indolicidin analog with a proline and tryptophan residue substituted with lysines showed more pronounced bilayer surface interactions, while Indolicidin and particularly an Indolicidin analog in which all prolines were replaced with alanine residues exhibited deeper insertion into the lipid bilayer. The colorimetric data demonstrated that more pronounced blue-red transitions were observed when the chromatic vesicles incorporated lipopolysaccharide (LPS) within the lipid bilayer, indicating that LPS promoted preferred binding and incorporation of the peptides at the lipid/water interface. The fluorescence quenching experiments further confirmed this outcome. The results indicate that the antibacterial activity of Indolicidin most likely requires initial binding to the LPS moieties within bacterial membranes, as well as disruption of the bilayer interface. The degree of hemolysis induced by the analogs, on the other hand, correlated to the extent of penetration into the hydrophobic core of the lipid assembly.
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structure and mechanism of action of an Indolicidin peptide derivative with improved activity against gram positive bacteria
Journal of Biological Chemistry, 2001Co-Authors: Carol L. Friedrich, Aleksander Patrzykat, Annett Rozek, Robert E. W. HancockAbstract:Abstract Indolicidin, an antimicrobial peptide with a unique amino acid sequence (ILPWKWPWWPWRR-NH2) is found in bovine neutrophils. A derivative of Indolicidin, CP10A, has alanine residues substituted for proline residues and has improved activity against Gram-positive organisms. Transmission electron microscopy of Staphylococcus aureus andStaphylococcus epidermidis treated with CP10A showed mesosome-like structures in the cytoplasm. The peptide at 2-fold the minimal inhibitory concentration did not show significant killing ofS. aureus ISP67 (a histidine, uridine, and thymidine auxotroph) but did show an early effect on histidine and uridine incorporation and, later, an effect on thymidine incorporation. Upon interaction with liposomes, detergents, and lipoteichoic acid, CP10A was shown by circular dichroism spectroscopy to undergo a change in secondary structure. Fluorescence spectroscopy indicated that the tryptophan residues were located at the hydrophobic/hydrophilic interface of liposomes and detergent micelles and were inaccessible to the aqueous quencher KI. The three-dimensional structure of CP10A in the lipid mimetic dodecylphosphocholine was determined using two-dimensional NMR methods and was characterized as a short, amphipathic helical structure, whereas Indolicidin was previously shown to have an extended structure. These studies have introduced a cationic peptide with a unique structure and an ability to interact with membranes and to affect intracellular synthesis of proteins, RNA, and DNA.
Palok Aich - One of the best experts on this subject based on the ideXlab platform.
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Comparative efficacy analysis of anti-microbial peptides, LL-37 and Indolicidin upon conjugation with CNT, in human monocytes
Journal of Nanobiotechnology, 2017Co-Authors: Biswaranjan Pradhan, Abhinav Sur, Dipanjan Guha, Krushna Chandra Murmu, Pratikshya Ray, Debashmita Das, Palok AichAbstract:Background Antimicrobial peptides (AMPs) have the potential to serve as an alternative to antibiotic. AMPs usually exert bactericidal activity via direct killing of microbial pathogens. Reports have proposed that by harnessing innate immune activation, AMPs can regulate pathogen invasion and may control infection. It has been reported that AMPs could be utilized to activate the innate mucosal immune response in order to eliminate pathogenic infections. This way of controlling pathogen infection, by activating host immunity, confers the potential to the select AMPs to alleviate the problem of antibiotic resistance. Among various AMPs tested LL-37 and Indolicidin, showed promise to be potential candidates for eliciting enhanced host innate immune responses. LL-37 and Indolicidin had exhibited substantial innate immune activation in both human and murine macrophages. Dosage for each of the AMPs, however, was high with adverse side effects. Results In this study, we reported that upon conjugation with carbon nanotubes (CNT), each AMP remained biologically functional at a concentration that was 1000-fold less than the dosage required for free AMP to remain active in the cells. Conclusions Current study also revealed that while Indolicidin induced signalling events mediated through the TNFRSF1A pathway in THP1 cells, followed by activation of NFκB and c-JUN pathways, treatment of cells with LL-37 induced signalling events by activating IL1R, with subsequent activation of NFκB and NFAT2. Thp1 cells, primed with CNT conjugated LL-37 or Indolicidin, are protected against Salmonella typhimurium infection at 16 h post challenge.
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comparative efficacy analysis of anti microbial peptides ll 37 and Indolicidin upon conjugation with cnt in human monocytes
Journal of Nanobiotechnology, 2017Co-Authors: Biswaranjan Pradhan, Abhinav Sur, Dipanjan Guha, Krushna Chandra Murmu, Pratikshya Ray, Debashmita Das, Palok AichAbstract:Antimicrobial peptides (AMPs) have the potential to serve as an alternative to antibiotic. AMPs usually exert bactericidal activity via direct killing of microbial pathogens. Reports have proposed that by harnessing innate immune activation, AMPs can regulate pathogen invasion and may control infection. It has been reported that AMPs could be utilized to activate the innate mucosal immune response in order to eliminate pathogenic infections. This way of controlling pathogen infection, by activating host immunity, confers the potential to the select AMPs to alleviate the problem of antibiotic resistance. Among various AMPs tested LL-37 and Indolicidin, showed promise to be potential candidates for eliciting enhanced host innate immune responses. LL-37 and Indolicidin had exhibited substantial innate immune activation in both human and murine macrophages. Dosage for each of the AMPs, however, was high with adverse side effects. In this study, we reported that upon conjugation with carbon nanotubes (CNT), each AMP remained biologically functional at a concentration that was 1000-fold less than the dosage required for free AMP to remain active in the cells. Current study also revealed that while Indolicidin induced signalling events mediated through the TNFRSF1A pathway in THP1 cells, followed by activation of NFκB and c-JUN pathways, treatment of cells with LL-37 induced signalling events by activating IL1R, with subsequent activation of NFκB and NFAT2. Thp1 cells, primed with CNT conjugated LL-37 or Indolicidin, are protected against Salmonella typhimurium infection at 16 h post challenge.
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MOESM3 of Comparative efficacy analysis of anti-microbial peptides, LL-37 and Indolicidin upon conjugation with CNT, in human monocytes
2017Co-Authors: Biswaranjan Pradhan, Abhinav Sur, Dipanjan Guha, Pratikshya Ray, Debashmita Das, Krushna Murmu, Palok AichAbstract:Additional file 3: Table S3. Expression of genes in terms of fold changes following treatment free and conjugated Indolicidin and other conditions
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Absorbance and fluorescence spectra and binding isotherm.
2015Co-Authors: Abhinav Sur, Biswaranjan Pradhan, Arka Banerjee, Palok AichAbstract:Representative (a) absorbance spectra of free Indolicidin (I), free CNT, free GNP, CNT conjugated I (CNT_I) and GNP conjugated (GNP_I) Indolicidin and fluorescence spectra of (b) free CNT, CNT-I, free I and free CNT spiked with Indolicidin and of (c) free GNP, GNP-I, free I and free GNP spiked with Indolicidin are shown. Spectra are labeled in the panels for easy identification. Binding isotherm of Indolicidin with CNT and GNP. Fraction of Indolicidin bound with (a) CNT and (c) GNP and Scatchard plot of binding of Indolicidin with (b) CNT and (d) GNP are shown. Panels (b) and (d) also listed the values of association constant and stoichiometry of binding. Standard deviations of the data are shown as error bars in the figure.
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SEM images.
2015Co-Authors: Abhinav Sur, Biswaranjan Pradhan, Arka Banerjee, Palok AichAbstract:Representative SEM micrographs of CNTs (panels a & b, scale 1 μm) and CNT-Indolicidin conjugates (panels c [scale 1μm] & d[scale 200 nm]) as well as GNPs (panles e & f, scale 200 nm) and GNP-Indolicidin conjugates (panels g [scale 2 μm] & h [scale 200 nm]) are shown.