当前位置： SCI文献检索 > ACS Infectious Diseases期刊下所有文献 > Targeting Bacterial Sortase A with Covalent Inhibitors: 27 New Starting Points for Structure-Based Hit-to-Lead Optimization.

Targeting Bacterial Sortase A with Covalent Inhibitors: 27 New Starting Points for Structure-Based Hit-to-Lead Optimization.

Abstract：

:Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of Staphylococcus aureus SrtA by screening a library of approximately 50 000 compounds using a FRET assay followed by NMR-based validation and binding reversibility analysis. Nineteen of these compounds displayed only moderate to weak cytotoxicity, with CC50 against NIH 3T3 mice fibroblast cells ranging from 12 to 740 μM. Analysis using covalent docking suggests that the inhibitors initially associate via hydrophobic interactions, followed by covalent bond formation between the SrtA active site cysteine and an electrophilic center of the inhibitor. The compounds represent good starting points that have the potential to be developed into broad spectrum antivirulence agents as exemplified by hit-to-lead optimization of one of the compounds.

journal_name

ACS Infect Dis

journal_title

ACS infectious diseases

authors

Jaudzems K,Kurbatska V,Je Kabsons A,Bobrovs R,Rudevica Z,Leonchiks A

doi

10.1021/acsinfecdis.9b00265

subject

Has Abstract

pub_date

2020-02-14 00:00:00

pages

186-194

issue

2

issn

2373-8227

journal_volume

6

pub_type

信件

相关文献

ACS Infectious Diseases文献大全
  • Vaginal Product Formulation Alters the Innate Antiviral Activity and Glycome of Cervicovaginal Fluids with Implications for Viral Susceptibility.

    abstract：:Glycosylated proteins (i.e., mucins, IgG) are important mediators of innate antiviral immunity in the vagina; however, our current knowledge of the role that glycan themselves play in genital immunity is relatively low. Herein, we evaluate the relationship between innate antiviral immunity and glycomic composition in ...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章,随机对照试验

    doi：10.1021/acsinfecdis.8b00157

    authors： Koppolu S,Wang L,Mathur A,Nigam JA,Dezzutti CS,Isaacs C,Meyn L,Bunge KE,Moncla BJ,Hillier SL,Rohan LC,Mahal LK

    更新日期：2018-11-09 00:00:00

  • Modification at the 2'-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity.

    abstract：:A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin was prepared and assayed for (i) their ability to inhibit protein synthesis by bacterial ribosomes and by engineered bacterial ribosomes carrying eukaryotic decoding A sites, ...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00128

    authors： Sati GC,Sarpe VA,Furukawa T,Mondal S,Mantovani M,Hobbie SN,Vasella A,Böttger EC,Crich D

    更新日期：2019-10-11 00:00:00

  • Chemical Warfare at the Microorganismal Level: A Closer Look at the Superoxide Dismutase Enzymes of Pathogens.

    abstract：:Superoxide anion radical is generated as a natural byproduct of aerobic metabolism but is also produced as part of the oxidative burst of the innate immune response design to kill pathogens. In living systems, superoxide is largely managed through superoxide dismutases (SODs), families of metalloenzymes that use Fe, M...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章,评审

    doi：10.1021/acsinfecdis.8b00026

    authors： Schatzman SS,Culotta VC

    更新日期：2018-06-08 00:00:00

  • Illicit Transport via Dipeptide Transporter Dpp is Irrelevant to the Efficacy of Negamycin in Mouse Thigh Models of Escherichia coli Infection.

    abstract：:Negamycin is a hydrophilic antimicrobial translation inhibitor that crosses the lipophilic inner membrane of Escherichia coli via at least two transport routes to reach its intracellular target. In a minimal salts medium, negamycin's peptidic nature allows illicit entry via a high-affinity route by hijacking the Dpp d...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.5b00027

    authors： McKinney DC,Bezdenejnih-Snyder N,Farrington K,Guo J,McLaughlin RE,Ruvinsky AM,Singh R,Basarab GS,Narayan S,Buurman ET

    更新日期：2015-05-08 00:00:00

  • Photodynamic Inactivation of ESKAPE Group Bacterial Pathogens in Planktonic and Biofilm Cultures Using Metallated Porphyrin-Doped Conjugated Polymer Nanoparticles.

    abstract：:Photodynamic inactivation (PDI) protocols using photoactive metallated porphyrin-doped conjugated polymer nanoparticles (CPNs) and blue light were developed to eliminate multidrug-resistant pathogens. CPNs-PDI protocols using varying particle concentrations and irradiation doses were tested against nine pathogenic bac...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.0c00268

    authors： Martínez SR,Ibarra LE,Ponzio RA,Forcone MV,Wendel AB,Chesta CA,Spesia MB,Palacios RE

    更新日期：2020-08-14 00:00:00

  • Rapid in Vitro Assessment of Clostridioides difficile Inhibition by Probiotics Using Dielectrophoresis to Quantify Cell Structure Alterations.

    abstract：:Clostridioides difficile (C. difficile) infection (CDI) is the primary cause of nosocomial antibiotic-associated diarrhea, with high recurrence rates following initial antibiotic treatment regimens. Restoration of the host gut microbiome through probiotic therapy is under investigation to reduce recurrence. Current in...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00415

    authors： Moore JH,Honrado C,Stagnaro V,Kolling G,Warren CA,Swami NS

    更新日期：2020-05-08 00:00:00

  • A Methyl 4-Oxo-4-phenylbut-2-enoate with in Vivo Activity against MRSA that Inhibits MenB in the Bacterial Menaquinone Biosynthesis Pathway.

    abstract：:4-Oxo-4-phenyl-but-2-enoates inhibit MenB, the 1,4-dihydroxyl-2-naphthoyl-CoA synthase in the bacterial menaquinone (MK) biosynthesis pathway, through the formation of an adduct with coenzyme A (CoA). Here, we show that the corresponding methyl butenoates have MIC values as low as 0.35-0.75 µg/mL against drug sensitiv...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.6b00023

    authors： Matarlo JS,Lu Y,Daryaee F,Daryaee T,Ruzsicska B,Walker SG,Tonge PJ

    更新日期：2016-05-13 00:00:00

  • Introduction of a Thio Functional Group to Diazabicyclooctane: An Effective Modification to Potentiate the Activity of β-Lactams against Gram-Negative Bacteria Producing Class A, C, and D Serine β-Lactamases.

    abstract：:By the emergence and worldwide spread of multi-drug-resistant Gram-negative bacteria, there have been growing demands for efficacious drugs to cure these resistant infections. The key mechanism for resistance to β-lactam antibiotics is the production of β-lactamases, which hydrolyze and deactivate β-lactams. Diazabicy...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.0c00560

    authors： Fujiu M,Yokoo K,Sato J,Shibuya S,Komano K,Kusano H,Sato S,Aoki T,Kohira N,Miyagawa S,Kawachi T,Yamawaki K

    更新日期：2020-11-13 00:00:00

  • Protein S-Palmitoylation Is Responsive to External Signals and Plays a Regulatory Role in Microneme Secretion in Plasmodium falciparum Merozoites.

    abstract：:Protein S-palmitoylation is an important post-translational modification (PTM) in blood stages of the malaria parasite, Plasmodium falciparum. S-palmitoylation refers to reversible covalent modification of cysteine residues of proteins by saturated fatty acids. In vivo, palmitoylation is regulated by concerted activit...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00321

    authors： Siddiqui MA,Singh S,Malhotra P,Chitnis CE

    更新日期：2020-03-13 00:00:00

  • Antisense Inhibitors Retain Activity in Pulmonary Models of Burkholderia Infection.

    abstract：:The Burkholderia cepacia complex is a group of Gram-negative bacteria that are opportunistic pathogens in immunocompromised individuals, such as those with cystic fibrosis (CF) or chronic granulomatous disease (CGD). Burkholderia are intrinsically resistant to many antibiotics and the lack of antibiotic development ne...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.7b00235

    authors： Daly SM,Sturge CR,Marshall-Batty KR,Felder-Scott CF,Jain R,Geller BL,Greenberg DE

    更新日期：2018-05-11 00:00:00

  • Development of an Enzyme-Mediated, Site-Specific Method to Conjugate Toll-Like Receptor 2 Agonists onto Protein Antigens: Toward a Broadly Protective, Four Component, Group A Streptococcal Self-Adjuvanting Lipoprotein-Fusion Combination Vaccine.

    abstract：:Subunit vaccines composed of protein antigens covalently attached to Toll-like receptor (TLR) agonists elicit superior immune responses compared to mixtures of antigens and TLR agonists. Among different conjugation approaches, enzyme-mediated ligation is one of the few that provides an opportunity for the generation o...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.0c00047

    authors： Xu Z,Rivera-Hernandez T,Moyle PM

    更新日期：2020-07-10 00:00:00

  • Biochemical Characterization of Respiratory Syncytial Virus RNA-Dependent RNA Polymerase Complex.

    abstract：:RNA-dependent RNA polymerases (RdRPs) from nonsegmented negative strand (NNS) RNA viruses perform both mRNA transcription and genome replication, and these activities are regulated by their interactions with RNA and other accessory proteins within the ribonucleoprotein (RNP) complex. Detailed biochemical characterizat...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.0c00554

    authors： Balakrishnan A,Price E,Luu C,Shaul J,Wartchow C,Cantwell J,Vo T,DiDonato M,Spraggon G,Hekmat-Nejad M

    更新日期：2020-10-09 00:00:00

  • Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients.

    abstract：:Burkholderia multivorans is a significant health threat to persons with cystic fibrosis (CF). Infections are difficult to treat as this pathogen is inherently resistant to multiple antibiotics. Susceptibility testing of isolates obtained from CF respiratory cultures revealed that single agents selected from different ...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.7b00020

    authors： Papp-Wallace KM,Becka SA,Zeiser ET,Ohuchi N,Mojica MF,Gatta JA,Falleni M,Tosi D,Borghi E,Winkler ML,Wilson BM,LiPuma JJ,Nukaga M,Bonomo RA

    更新日期：2017-07-14 00:00:00

  • Discovery and Mechanistic Study of a Novel Human-Stimulator-of-Interferon-Genes Agonist.

    abstract：:Stimulator of interferon genes (STING) is an integral ER-membrane protein that can be activated by 2'3'-cGAMP synthesized by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) upon binding of double-stranded DNA. It activates interferon (IFN) and inflammatory cytokine responses to defend against in...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00010

    authors： Zhang X,Liu B,Tang L,Su Q,Hwang N,Sehgal M,Cheng J,Ma J,Zhang X,Tan Y,Zhou Y,Duan Z,DeFilippis VR,Viswanathan U,Kulp J,Du Y,Guo JT,Chang J

    更新日期：2019-07-12 00:00:00

  • Diaza-anthracene Antibiotics from a Freshwater-Derived Actinomycete with Selective Antibacterial Activity toward Mycobacterium tuberculosis.

    abstract：:Multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis are resistant to first- and second-line drug regimens and resulted in 210,000 fatalities in 2013. In the current study, we screened a library of aquatic bacterial natural product fractions for their ability to inhibit this pathogen. A frac...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.5b00005

    authors： Mullowney MW,Hwang CH,Newsome AG,Wei X,Tanouye U,Wan B,Carlson S,Barranis NJ,hAinmhire E,Chen WL,Krishnamoorthy K,White J,Blair R,Lee H,Burdette JE,Rathod PK,Parish T,Cho S,Franzblau SG,Murphy BT

    更新日期：2015-04-10 00:00:00

  • Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic Evaluation of the Current Antimalarial Targets Portfolio.

    abstract：:Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgenc...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.7b00211

    authors： Chaparro MJ,Calderón F,Castañeda P,Fernández-Alvaro E,Gabarró R,Gamo FJ,Gómez-Lorenzo MG,Martín J,Fernández E

    更新日期：2018-04-13 00:00:00

  • Molecular Mechanism of Avibactam-Mediated β-Lactamase Inhibition.

    abstract：:Emerging β-lactamase-mediated resistance is threatening the clinical utility of the single most prominent class of antibacterial agents used in medicine, the β-lactams. The diazabicyclooctane avibactam is able to inhibit a wider range of serine β-lactamases than has been previously observed with β-lactamase inhibitors...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.5b00007

    authors： King DT,King AM,Lal SM,Wright GD,Strynadka NC

    更新日期：2015-04-10 00:00:00

  • Interaction of a Model Peptide on Gram Negative and Gram Positive Bacterial Sliding Clamps.

    abstract：:Bacterial sliding clamps control the access of DNA polymerases to the replication fork and are appealing targets for antibacterial drug development. It is therefore essential to decipher the polymerase-clamp binding mode across various bacterial species. Here, two residues of the E. coli clamp binding pocket, EcS346 a...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00089

    authors： André C,Martiel I,Wolff P,Landolfo M,Lorber B,Silva da Veiga C,Dejaegere A,Dumas P,Guichard G,Oliéric V,Wagner J,Burnouf DY

    更新日期：2019-06-14 00:00:00

  • N-Myristoylation as a Drug Target in Malaria: Exploring the Role of N-Myristoyltransferase Substrates in the Inhibitor Mode of Action.

    abstract：:Malaria continues to be a significant cause of death and morbidity worldwide, and there is a need for new antimalarial drugs with novel targets. We have focused as a potential target for drug development on N-myristoyl transferase (NMT), an enzyme that acylates a wide range of substrate proteins. The NMT substrates in...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章,评审

    doi：10.1021/acsinfecdis.7b00203

    authors： Schlott AC,Holder AA,Tate EW

    更新日期：2018-04-13 00:00:00

  • Preclinical Antiviral Testing for Dengue Virus Infection in Mouse Models and Its Association with Clinical Studies.

    abstract：:At present, there is no licensed antiviral drug against dengue virus (DENV) infection. Mouse models of DENV infection have been widely used for preclinical evaluation of antivirals. However, only in a few instances so far have the data obtained from preclinical mouse model testing been associated with data from clinic...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章,评审

    doi：10.1021/acsinfecdis.8b00054

    authors： Watanabe S,Low JG,Vasudevan SG

    更新日期：2018-07-13 00:00:00

  • Targeted Inhibition of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 with a Constrained J Domain-Derived Disruptor Peptide.

    abstract：:To explore the possibility of constrained peptides to target Plasmodium-infected cells, we designed a J domain mimetic derived from Plasmodium falciparum calcium-dependent protein kinase 1 ( PfCDPK1) as a strategy to disrupt J domain binding and inhibit PfCDPK1 activity. The J domain disruptor (JDD) peptide was confor...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.8b00347

    authors： Flaherty BR,Ho TG,Schmidt SH,Herberg FW,Peterson DS,Kennedy EJ

    更新日期：2019-04-12 00:00:00

  • Violacein Targets the Cytoplasmic Membrane of Bacteria.

    abstract：:Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens. Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.8b00245

    authors： Cauz ACG,Carretero GPB,Saraiva GKV,Park P,Mortara L,Cuccovia IM,Brocchi M,Gueiros-Filho FJ

    更新日期：2019-04-12 00:00:00

  • Zika Virus: Diagnosis, Therapeutics, and Vaccine.

    abstract：:The current explosive epidemic of Zika virus in South and Central America, as well as the Caribbean, poses a global public health emergency. Here we comment on the challenges on development of better diagnosis and potential therapeutics and vaccine for Zika virus. ...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.6b00030

    authors： Shan C,Xie X,Barrett AD,Garcia-Blanco MA,Tesh RB,Vasconcelos PF,Vasilakis N,Weaver SC,Shi PY

    更新日期：2016-03-11 00:00:00

  • Efficient Blocking of Enterovirus 71 Infection by Heparan Sulfate Analogues Acting as Decoy Receptors.

    abstract：:Enterovirus 71 (EV71) is a major etiological agent of hand, foot, and mouth disease, for which there is no antiviral therapy. We have developed densely sulfated disaccharide heparan sulfate (HS) analogues that are potent small molecule inhibitors of EV71 infection, binding to the viral capsid and acting as decoy recep...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00070

    authors： Earley DF,Bailly B,Maggioni A,Kundur AR,Thomson RJ,Chang CW,von Itzstein M

    更新日期：2019-10-11 00:00:00

  • Inhibiting Iron Mobilization from Bacterioferritin in Pseudomonas aeruginosa Impairs Biofilm Formation Irrespective of Environmental Iron Availability.

    abstract：:Although iron is essential for bacteria, the nutrient presents problems of toxicity and solubility. Bacteria circumvent these problems with the aid of iron storage proteins where Fe3+ is deposited and, when necessary, mobilized as Fe2+ for metabolic requirements. In Pseudomonas aeruginosa, Fe3+ is compartmentalized in...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00398

    authors： Soldano A,Yao H,Chandler JR,Rivera M

    更新日期：2020-03-13 00:00:00

  • Toward Broad Spectrum Dihydrofolate Reductase Inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin Resistant Staphylococcus aureus.

    abstract：:The spread of plasmid borne resistance enzymes in clinical Staphylococcus aureus isolates is rendering trimethoprim and iclaprim, both inhibitors of dihydrofolate reductase (DHFR), ineffective. Continued exploitation of these targets will require compounds that can broadly inhibit these resistance-conferring isoforms....

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00222

    authors： Reeve SM,Si D,Krucinska J,Yan Y,Viswanathan K,Wang S,Holt GT,Frenkel MS,Ojewole AA,Estrada A,Agabiti SS,Alverson JB,Gibson ND,Priestley ND,Wiemer AJ,Donald BR,Wright DL

    更新日期：2019-11-08 00:00:00

  • Discrimination of Escherichia coli and Shigella spp. by Nuclear Magnetic Resonance Based Metabolomic Characterization of Culture Media.

    abstract：:Dysentery is a major health threat that dramatically impacts childhood morbidity and mortality in developing countries. Various pathogenic agents cause dysentery, such as Shigella spp. and Escherichia coli, which are very closely related if not identical species. Sensitive and precise detection and identification of t...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.9b00199

    authors： Rautureau GJP,Palama TL,Canard I,Mirande C,Chatellier S,van Belkum A,Elena-Herrmann B

    更新日期：2019-11-08 00:00:00

  • Phylogenetic and Biochemical Analyses of Mycobacterial l,d-Transpeptidases Reveal a Distinct Enzyme Class That Is Preferentially Acylated by Meropenem.

    abstract：:The genomes of diverse mycobacterial species encode multiple proteins with the canonical l,d-transpeptidase (Ldt) sequence motif. The reason for this apparent redundancy is not well understood, but evidence suggests paralogous Ldts may serve niche roles in maintaining and/or remodeling mycobacterial peptidoglycan. We ...

    journal_title：ACS infectious diseases

    pub_type： 信件

    doi：10.1021/acsinfecdis.9b00234

    authors： Zandi TA,Marshburn RL,Stateler PK,Brammer Basta LA

    更新日期：2019-12-13 00:00:00

  • Investigational Studies on a Hit Compound Cyclopropane-Carboxylic Acid Derivative Targeting O-Acetylserine Sulfhydrylase as a Colistin Adjuvant.

    abstract：:Antibacterial adjuvants are of great significance, since they allow the therapeutic dose of conventional antibiotics to be lowered and reduce the insurgence of antibiotic resistance. Herein, we report that an O-acetylserine sulfhydrylase (OASS) inhibitor can be used as a colistin adjuvant to treat infections caused by...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.0c00378

    authors： Annunziato G,Spadini C,Franko N,Storici P,Demitri N,Pieroni M,Flisi S,Rosati L,Iannarelli M,Marchetti M,Magalhaes J,Bettati S,Mozzarelli A,Cabassi CS,Campanini B,Costantino G

    更新日期：2021-01-29 00:00:00

  • Gene Expression Variability Underlies Adaptive Resistance in Phenotypically Heterogeneous Bacterial Populations.

    abstract：:The root cause of the antibiotic resistance crisis is the ability of bacteria to evolve resistance to a multitude of antibiotics and other environmental toxins. The regulation of adaptation is difficult to pinpoint due to extensive phenotypic heterogeneity arising during evolution. Here, we investigate the mechanisms ...

    journal_title：ACS infectious diseases

    pub_type： 杂志文章

    doi：10.1021/acsinfecdis.5b00095

    authors： Erickson KE,Otoupal PB,Chatterjee A

    更新日期：2015-11-13 00:00:00