How many antimicrobial peptide molecules kill a bacterium? The case of PMAP-23.

Abstract:

:Antimicrobial peptides (AMPs) kill bacteria mainly through the perturbation of their membranes and are promising compounds to fight drug resistance. Models of the mechanism of AMPs-induced membrane perturbation were developed based on experiments in liposomes, but their relevance for bacterial killing is debated. We determined the association of an analogue of the AMP PMAP-23 to Escherichia coli cells, under the same experimental conditions used to measure bactericidal activity. Killing took place only when bound peptides completely saturated bacterial membranes (10(6)-10(7) bound peptides per cell), indicating that the "carpet" model for the perturbation of artificial bilayers is representative of what happens in real bacteria. This finding supports the view that, at least for this peptide, a microbicidal mechanism is possible in vivo only at micromolar total peptide concentrations. We also showed that, notwithstanding their simplicity, liposomes represent a reliable model to characterize AMPs partition in bacterial membranes.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Roversi D,Luca V,Aureli S,Park Y,Mangoni ML,Stella L

doi

10.1021/cb500426r

subject

Has Abstract

pub_date

2014-09-19 00:00:00

pages

2003-7

issue

9

eissn

1554-8929

issn

1554-8937

journal_volume

9

pub_type

信件
  • Novel modifications in RNA.

    abstract::The past several years have seen numerous reports of new chemical modifications for use in RNA. In addition, in that time period, we have seen the discovery of several previously unknown naturally occurring modifications that impart novel properties on the parent RNAs. In this review, we describe recent discoveries in...

    journal_title:ACS chemical biology

    pub_type: 杂志文章,评审

    doi:10.1021/cb200422t

    authors: Phelps K,Morris A,Beal PA

    更新日期:2012-01-20 00:00:00

  • Comparative chemogenomics to examine the mechanism of action of dna-targeted platinum-acridine anticancer agents.

    abstract::Platinum-based drugs have been used to successfully treat diverse cancers for several decades. Cisplatin, the original compound of this class, cross-links DNA, resulting in cell cycle arrest and cell death via apoptosis. Cisplatin is effective against several tumor types, yet it exhibits toxic side effects and tumors ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb300320d

    authors: Cheung-Ong K,Song KT,Ma Z,Shabtai D,Lee AY,Gallo D,Heisler LE,Brown GW,Bierbach U,Giaever G,Nislow C

    更新日期:2012-11-16 00:00:00

  • Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.

    abstract::Designed second mitochondrial activator of caspases (Smac) mimetics based on an accessible [7,5]-bicyclic scaffold bind to and antagonize protein interactions involving the inhibitor of apoptosis (IAP) proteins, X-chromosome-linked IAP (XIAP), melanoma IAP (ML-IAP), and c-IAPs 1 and 2 (cIAP1 and cIAP2). The design rat...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb600276q

    authors: Zobel K,Wang L,Varfolomeev E,Franklin MC,Elliott LO,Wallweber HJ,Okawa DC,Flygare JA,Vucic D,Fairbrother WJ,Deshayes K

    更新日期:2006-09-19 00:00:00

  • Use of calculated cation-pi binding energies to predict relative strengths of nicotinic acetylcholine receptor agonists.

    abstract::Agonists and antagonists of the nicotinic acetylcholine receptor (nAChR) are used to treat nicotine addiction, neuromuscular disorders, and neurological diseases. In designing small molecule therapeutics with the nAChR as a target, it is useful to identify chemical parameters that correlate with ability to activate th...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb800189y

    authors: Tantama M,Licht S

    更新日期:2008-11-21 00:00:00

  • Cell Permeable Ratiometric Fluorescent Sensors for Imaging Phosphoinositides.

    abstract::Phosphoinositides are critical cell-signal mediators present on the plasma membrane. The dynamic change of phosphoinositide concentrations on the membrane including clustering and declustering mediates signal transduction. The importance of phosphoinositides is scored by the fact that they participate in almost all ce...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.6b00067

    authors: Mondal S,Rakshit A,Pal S,Datta A

    更新日期:2016-07-15 00:00:00

  • Imaging the lipidome: omega-alkynyl fatty acids for detection and cellular visualization of lipid-modified proteins.

    abstract::Fatty acylation or lipid modification of proteins controls their cellular activation and diverse roles in physiology. It mediates protein-protein and protein-membrane interactions and plays an important role in regulating cellular signaling pathways. Currently, there is need for visualizing lipid modifications of prot...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb900085z

    authors: Hannoush RN,Arenas-Ramirez N

    更新日期:2009-07-17 00:00:00

  • Elucidating the Origin of Long Residence Time Binding for Inhibitors of the Metalloprotease Thermolysin.

    abstract::Kinetic parameters of protein-ligand interactions are progressively acknowledged as valuable information for rational drug discovery. However, a targeted optimization of binding kinetics is not easy to achieve, and further systematic studies are necessary to increase the understanding about molecular mechanisms involv...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.6b00979

    authors: Cramer J,Krimmer SG,Fridh V,Wulsdorf T,Karlsson R,Heine A,Klebe G

    更新日期:2017-01-20 00:00:00

  • Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker.

    abstract::Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology. Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conj...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.8b00414

    authors: Qin K,Zhu Y,Qin W,Gao J,Shao X,Wang YL,Zhou W,Wang C,Chen X

    更新日期:2018-08-17 00:00:00

  • A synthetic recursive "+1" pathway for carbon chain elongation.

    abstract::Nature uses four methods of carbon chain elongation for the production of 2-ketoacids, fatty acids, polyketides, and isoprenoids. Using a combination of quantum mechanical (QM) modeling, protein-substrate modeling, and protein and metabolic engineering, we have engineered the enzymes involved in leucine biosynthesis f...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb200313e

    authors: Marcheschi RJ,Li H,Zhang K,Noey EL,Kim S,Chaubey A,Houk KN,Liao JC

    更新日期:2012-04-20 00:00:00

  • Transferrin Cycle and Clinical Roles of Citrate and Ascorbate in Improved Iron Metabolism.

    abstract::Fe(III) delivery from blood plasma to cells via the transferrin (Tf) cycle was studied intensively due to its crucial role in Fe homeostasis. Tf-cycle disruptions are linked to anemia, infections, immunodeficiency, and neurodegeneration. Biolayer interferometry (BLI) enabled direct kinetic and thermodynamic measuremen...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.8b01100

    authors: Levina A,Lay PA

    更新日期:2019-05-17 00:00:00

  • Comprehensive Derivatization of Thioviridamides by Heterologous Expression.

    abstract::New technology for the derivatization of peptide natural products is required for drug development. Despite the recent advances in the genome sequencing technique enabling us to search for the biosynthetic genes for wide variety of natural products, the technical methods to get access to them are limited. A class of R...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00330

    authors: Kudo K,Koiwai H,Kagaya N,Nishiyama M,Kuzuyama T,Shin-Ya K,Ikeda H

    更新日期:2019-06-21 00:00:00

  • siRNA screen identifies the phosphatase acting on the G protein-coupled thyrotropin-releasing hormone receptor.

    abstract::G protein-coupled receptors (GPCRs) are an ubiquitously expressed class of transmembrane proteins involved in the signal transduction of neurotransmitters, hormones and various other ligands. Their signaling output is desensitized by mechanisms involving phosphorylation, internalization, and dissociation from G protei...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb3004513

    authors: Gehret AU,Hinkle PM

    更新日期:2013-03-15 00:00:00

  • Botryllamides: natural product inhibitors of ABCG2.

    abstract::ABCG2 is a membrane-localized, human transporter protein that has been demonstrated to reduce the intracellular accumulation of substrates through ATP-dependent efflux. Highly expressed in placental syncytiotrophoblasts, brain microvasculature, and the gastrointestinal tract, ABCG2 has been shown to mediate normal tis...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb900134c

    authors: Henrich CJ,Robey RW,Takada K,Bokesch HR,Bates SE,Shukla S,Ambudkar SV,McMahon JB,Gustafson KR

    更新日期:2009-08-21 00:00:00

  • An unbiased approach to identify endogenous substrates of "histone" deacetylase 8.

    abstract::Despite being extensively characterized structurally and biochemically, the functional role of histone deacetylase 8 (HDAC8) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics method...

    journal_title:ACS chemical biology

    pub_type: 信件

    doi:10.1021/cb500492r

    authors: Olson DE,Udeshi ND,Wolfson NA,Pitcairn CA,Sullivan ED,Jaffe JD,Svinkina T,Natoli T,Lu X,Paulk J,McCarren P,Wagner FF,Barker D,Howe E,Lazzaro F,Gale JP,Zhang YL,Subramanian A,Fierke CA,Carr SA,Holson EB

    更新日期:2014-10-17 00:00:00

  • Synthetic lethal compound combinations reveal a fundamental connection between wall teichoic acid and peptidoglycan biosyntheses in Staphylococcus aureus.

    abstract::Methicillin resistance in Staphylococcus aureus depends on the production of mecA, which encodes penicillin-binding protein 2A (PBP2A), an acquired peptidoglycan transpeptidase (TP) with reduced susceptibility to β-lactam antibiotics. PBP2A cross-links nascent peptidoglycan when the native TPs are inhibited by β-lacta...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb100269f

    authors: Campbell J,Singh AK,Santa Maria JP Jr,Kim Y,Brown S,Swoboda JG,Mylonakis E,Wilkinson BJ,Walker S

    更新日期:2011-01-21 00:00:00

  • Formylglycine, a post-translationally generated residue with unique catalytic capabilities and biotechnology applications.

    abstract::Formylglycine (fGly) is a catalytically essential residue found almost exclusively in the active sites of type I sulfatases. Formed by post-translational oxidation of cysteine or serine side chains, this aldehyde-functionalized residue participates in a unique and highly efficient catalytic mechanism for sulfate ester...

    journal_title:ACS chemical biology

    pub_type: 杂志文章,评审

    doi:10.1021/cb500897w

    authors: Appel MJ,Bertozzi CR

    更新日期:2015-01-16 00:00:00

  • Identification of Compounds That Decrease Glioblastoma Growth and Glucose Uptake in Vitro.

    abstract::Tumor heterogeneity has hampered the development of novel effective therapeutic options for aggressive cancers, including the deadly primary adult brain tumor glioblastoma (GBM). Intratumoral heterogeneity is partially attributed to the tumor initiating cell (TIC) subset that contains highly tumorigenic, stem-like cel...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.8b00251

    authors: Libby CJ,Zhang S,Benavides GA,Scott SE,Li Y,Redmann M,Tran AN,Otamias A,Darley-Usmar V,Napierala M,Zhang J,Augelli-Szafran CE,Zhang W,Hjelmeland AB

    更新日期:2018-08-17 00:00:00

  • HIV-1 Env-Dependent Cell Killing by Bifunctional Small-Molecule/Peptide Conjugates.

    abstract::A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.0c00888

    authors: Gaffney A,Nangarlia A,Ang CG,Gossert S,Rashad Ahmed AA,Hossain MA,Abrams CF,Smith AB 3rd,Chaiken I

    更新日期:2021-01-15 00:00:00

  • Features of modularly assembled compounds that impart bioactivity against an RNA target.

    abstract::Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell-permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb400265y

    authors: Rzuczek SG,Gao Y,Tang ZZ,Thornton CA,Kodadek T,Disney MD

    更新日期:2013-10-18 00:00:00

  • Multiple Chemical Inducible Tal Effectors for Genome Editing and Transcription Activation.

    abstract::Inducible modulation is often required for precise investigations and manipulations of dynamic biological processes. Transcription activator-like effectors (TALEs) provide a powerful tool for targeted gene editing and transcriptional programming. We designed a series of chemical inducible systems by coupling TALEs wit...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00606

    authors: Zhao C,Zhang Y,Zhao Y,Ying Y,Ai R,Zhang J,Wang Y

    更新日期:2018-03-16 00:00:00

  • Structural Insights into the Interaction of Clinically Relevant Phosphorothioate mRNA Cap Analogs with Translation Initiation Factor 4E Reveal Stabilization via Electrostatic Thio-Effect.

    abstract::mRNA-based therapies and vaccines constitute a disruptive technology with the potential to revolutionize modern medicine. Chemically modified 5' cap structures have provided access to mRNAs with superior translational properties that could benefit the currently flourishing mRNA field. Prime examples of compounds that ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.0c00864

    authors: Warminski M,Kowalska J,Nowak E,Kubacka D,Tibble R,Kasprzyk R,Sikorski PJ,Gross JD,Nowotny M,Jemielity J

    更新日期:2021-01-13 00:00:00

  • A biosynthetic strategy for re-engineering the Staphylococcus aureus cell wall with non-native small molecules.

    abstract::Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. Here we report that the cell wall of S. aureus can be covalently re-engineered to contain non-native small molecules. This process makes use of endogenous levels of the bacterial enzyme sortase A (...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb100195d

    authors: Nelson JW,Chamessian AG,McEnaney PJ,Murelli RP,Kazmierczak BI,Spiegel DA

    更新日期:2010-12-17 00:00:00

  • On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7.

    abstract::The Siglec family of sialic acid-binding proteins are differentially expressed on white blood cells of the immune system and represent an attractive class of targets for cell-directed therapy. Nanoparticles decorated with high-affinity Siglec ligands show promise for delivering cargo to Siglec-bearing cells, but this ...

    journal_title:ACS chemical biology

    pub_type: 信件

    doi:10.1021/cb400125w

    authors: Rillahan CD,Schwartz E,Rademacher C,McBride R,Rangarajan J,Fokin VV,Paulson JC

    更新日期:2013-07-19 00:00:00

  • Activation of the NLRP3 Inflammasome by Hyaboron, a New Asymmetric Boron-Containing Macrodiolide from the Myxobacterium Hyalangium minutum.

    abstract::A Natural Compound Library containing myxobacterial secondary metabolites was screened in murine macrophages for novel activators of IL-1β maturation and secretion. The most potent of three hits in total was a so far undescribed metabolite, which was identified from the myxobacterium Hyalangium minutum strain Hym3. Wh...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.8b00659

    authors: Surup F,Chauhan D,Niggemann J,Bartok E,Herrmann J,Keck M,Zander W,Stadler M,Hornung V,Müller R

    更新日期:2018-10-19 00:00:00

  • A chemical genetic approach for covalent inhibition of analogue-sensitive aurora kinase.

    abstract::The perturbation of protein kinases with small organic molecules is a powerful approach to dissect kinase function in complex biological systems. Covalent kinase inhibitors that target thiols in the ATP binding pocket of the kinase domain proved to be ideal reagents for the investigation of highly dynamic cellular pro...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb200465c

    authors: Koch A,Rode HB,Richters A,Rauh D,Hauf S

    更新日期:2012-04-20 00:00:00

  • Peripheral protein organization and its influence on lipid diffusion in biomimetic membranes.

    abstract::Protein organization on biomembranes and their dynamics are essential for cellular function. It is not clear, however, how protein binding may influence the assembly of underlying lipids or how the membrane structure leads to functional protein organization. Toward this goal, we investigated the effects of annexin a5 ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb900303s

    authors: Vats K,Knutson K,Hinderliter A,Sheets ED

    更新日期:2010-04-16 00:00:00

  • Chemical Modulation of Human Mitochondrial ClpP: Potential Application in Cancer Therapeutics.

    abstract::The human ClpP proteolytic complex (HsClpP) is a serine protease located in the mitochondrial matrix and participates in the maintenance of the mitochondrial proteome among other cellular functions. HsClpP typically forms a multimeric complex with the AAA+ protein unfoldase HsClpX. Notably, compared to that of normal,...

    journal_title:ACS chemical biology

    pub_type: 杂志文章,评审

    doi:10.1021/acschembio.9b00347

    authors: Wong KS,Houry WA

    更新日期:2019-11-15 00:00:00

  • Replacing Mn(2+) with Co(2+) in human arginase i enhances cytotoxicity toward l-arginine auxotrophic cancer cell lines.

    abstract::Replacing the two Mn(2+) ions normally present in human Arginase I with Co(2+) resulted in a significantly lowered K(M) value without a concomitant reduction in k(cat). In addition, the pH dependence of the reaction was shifted from a pK(a) of 8.5 to a pK(a) of 7.5. The combination of these effects led to a 10-fold in...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb900267j

    authors: Stone EM,Glazer ES,Chantranupong L,Cherukuri P,Breece RM,Tierney DL,Curley SA,Iverson BL,Georgiou G

    更新日期:2010-03-19 00:00:00

  • Identification of pim kinases as novel targets for PJ34 with confounding effects in PARP biology.

    abstract::Small molecules are widely used in chemical biology without complete knowledge of their target profile, at risk of deriving conclusions that ignore potential confounding effects from unknown off-target interactions. The prediction and further experimental confirmation of novel affinities for PJ34 on Pim1 (IC(50) = 3.7...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb300317y

    authors: Antolín AA,Jalencas X,Yélamos J,Mestres J

    更新日期:2012-12-21 00:00:00

  • Steric restrictions of RISC in RNA interference identified with size-expanded RNA nucleobases.

    abstract::Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modifie...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb300174c

    authors: Hernández AR,Peterson LW,Kool ET

    更新日期:2012-08-17 00:00:00