Selection and characterization of human antibodies neutralizing Bacillus anthracis toxin.

Abstract:

:A less than adequate therapeutic plan for the treatment of anthrax in the 2001 bioterrorism attacks has highlighted the importance of developing alternative or complementary therapeutic approaches for biothreat agents. In these regards passive immunization possesses several important advantages over active vaccination and the use of antibiotics, as it can provide immediate protection against Bacillus anthracis. Herein, we report the selection and characterization of several human monoclonal neutralizing antibodies against the toxin of B. anthracis from a phage displayed human scFv library. In total 15 clones were selected with distinct sequences and high specificity to protective antigen and thus were the subject of a series of both biophysical and cell-based cytotoxicity assays. From this panel of antibodies a set of neutralizing antibodies were identified, of which clone A8 recognizes the lethal (and/or edema) factor binding domain, and clones F1, G11, and G12 recognize the cellular receptor binding domain found within the protective antigen. It was noted that all clones distinguish a conformational epitope existing on the protective antigen; this steric relationship was uncovered using a sequential epitope mapping approach. For each neutralizing antibody, the kinetic constants were determined by surface plasmon resonance, while the potency of protection was established using a two-tier macrophage cytotoxicity assay. Among the neutralizing antibodies identified, clone F1 possessed the highest affinity to protective antigen, and provided superior protection from lethal toxin in the cell cytotoxicity assay. The data presented provide the ever-growing arsenal of immunological and functional analysis of monoclonal antibodies to the exotoxins of anthrax. In addition it grants new candidates for the prophylaxis and therapeutic treatment against this toxin.

journal_name

Bioorg Med Chem

authors

Zhou B,Carney C,Janda KD

doi

10.1016/j.bmc.2007.11.001

subject

Has Abstract

pub_date

2008-02-15 00:00:00

pages

1903-13

issue

4

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(07)00968-6

journal_volume

16

pub_type

杂志文章
  • A genetically selected cyclic peptide inhibitor of BCL6 homodimerization.

    abstract::We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS library of 3.2 million cyclic hexapeptides in combination with a bacterial reverse two-hybrid system. This cyclic peptide is shown to bind the BTB domain of BCL6, disrupts its h...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.03.012

    authors: Osher EL,Castillo F,Elumalai N,Waring MJ,Pairaudeau G,Tavassoli A

    更新日期:2018-07-15 00:00:00

  • Characterization of chemical, radiochemical and optical properties of a dual-labeled MMP-9 targeting peptide.

    abstract::Optical imaging possesses similar sensitivity to nuclear imaging and has led to the emergence of multimodal approaches with dual-labeled nuclear/near-infrared (NIR) agents. The growing impact of (68)Ga (t(1/2)=68 min) labeled peptides on preclinical and clinical research offers a promising opportunity to merge the hig...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.04.054

    authors: Azhdarinia A,Wilganowski N,Robinson H,Ghosh P,Kwon S,Lazard ZW,Davis AR,Olmsted-Davis E,Sevick-Muraca EM

    更新日期:2011-06-15 00:00:00

  • Design, synthesis and tumor cell growth inhibitory activity of 3-nitro-2H-cheromene derivatives as histone deacetylaes inhibitors.

    abstract::As a continuous research for the discovery of coumarin-based targeted anticancer agents, we designed and synthesized a series of novel histone deacetylases (HDAC) inhibitors using the 8-ethoxy-3-nitro-2H-chromene as the surface binding or cap group, linear dicarboxylic acid or ω-amino acid moiety with different length...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.05.062

    authors: Tan S,He F,Kong T,Wu J,Liu Z

    更新日期:2017-08-01 00:00:00

  • Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 4: hyperbolic activation of rat liver microsomal NADPH-cytochrome C reductase by the novel acetylator 7,8-diacetoxy-4-methylcoumarin.

    abstract::The effect of 7,8-diacetoxy-4-methylcoumarin (DAMC) has been studied on hepatic NADPH cytochrome C reductase-- an enzyme participating in the microsomal electron transport. The preincubation of liver microsomes with DAMC resulted in a time-dependent activation of NADPH cytochrome C reductase. The catalytic activity of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(98)00228-4

    authors: Raj HG,Parmar VS,Jain SC,Goel S,Singh A,Tyagi YK,Jha HN,Olsen CE,Wengel J

    更新日期:1999-02-01 00:00:00

  • Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents.

    abstract::Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contribu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.12.019

    authors: Peprah K,Zhu XY,Eyunni SV,Setola V,Roth BL,Ablordeppey SY

    更新日期:2012-02-01 00:00:00

  • Synthesis of 1-D- and 1-L-myo-inosityl 2-N-acetamido-2-deoxy-alpha-D-glucopyranoside establishes substrate specificity of the Mycobacterium tuberculosis enzyme AcGI deacetylase.

    abstract::Mycothiol (MSH, 1-D-myo-inosityl 2-(N-acetyl-L-cysteinyl)amido-2-deoxy-alpha-D-glucopyranoside) is the principal low molecular weight thiol in actinomycetes. The enzyme 1-D-myo-inosityl 2-N-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase (AcGI deacetylase) is involved in the biosynthesis of MSH and forms the fre...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(03)00154-8

    authors: Nicholas GM,Eckman LL,Kovác P,Otero-Quintero S,Bewley CA

    更新日期:2003-06-12 00:00:00

  • Design, synthesis, in vitro, and in silico studies of novel diarylimidazole-1,2,3-triazole hybrids as potent α-glucosidase inhibitors.

    abstract::In this work, new derivatives of diarylimidazole-1,2,3-triazole 7a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity. All compounds showed potent inhibitory activity in the range of IC50 = 90.4-246.7 µM comparing with acarbose as the standard drug (IC50 = 750.0 µM). Among...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.115148

    authors: Saeedi M,Mohammadi-Khanaposhtani M,Asgari MS,Eghbalnejad N,Imanparast S,Faramarzi MA,Larijani B,Mahdavi M,Akbarzadeh T

    更新日期:2019-12-01 00:00:00

  • Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies.

    abstract::A series of 10 new 5-[2-(substituted sulfamoyl)-4,5-dimethoxy-benzyl]-4aryl-s-triazole-3-thiones were synthesized and evaluated for in vitro antifungal and antibacterial activity. All compounds tested showed significant antifungal activity against all the micromycetes, compared to the commercial fungicide bifonazole. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.10.082

    authors: Ezabadi IR,Camoutsis C,Zoumpoulakis P,Geronikaki A,Soković M,Glamocilija J,Cirić A

    更新日期:2008-02-01 00:00:00

  • Identification of a novel hormone sensitive lipase inhibitor with a reduced potential of reactive metabolites formation.

    abstract::Hormone sensitive lipase (HSL) has emerged as an attractive target for the treatment of dyslipidemia. We previously reported compound 1 as a potent and orally active HSL inhibitor. Although an attractive profile was demonstrated, subsequent studies revealed that compound 1 has a bioactivation liability. The oxygen-car...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.02.045

    authors: Ogiyama T,Yamaguchi M,Kurikawa N,Honzumi S,Yamamoto Y,Sugiyama D,Takakusa H,Inoue SI

    更新日期:2017-04-01 00:00:00

  • Synthetic strategies toward carbocyclic purine-pyrimidine hybrid nucleosides.

    abstract::The blending of key structural features from the purine and pyrimidine nucleobase scaffolds gives rise to a new class of hybrid nucleosides. The purine-pyrimidine hybrid nucleosides can be viewed as either N-3 ribosylated purines or 5,6-disubstituted pyrimidines, thus recognition by both purine- and pyrimidine-metabol...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.06.039

    authors: Sadler JM,Mosley SL,Dorgan KM,Zhou ZS,Seley-Radtke KL

    更新日期:2009-08-01 00:00:00

  • Design, synthesis, conformational analysis, and biological studies of urotensin-II lactam analogues.

    abstract::Human urotensin II (hU-II; H-Glu-Thr-Pro-Asp-cyclo[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) is a disulfide bridged undecapeptide recently identified as the ligand of an orphan G protein-coupled receptor. hU-II has been described as the most potent vasoconstrictor compound identified to date. With the aim of replacing the disu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00372-3

    authors: Grieco P,Carotenuto A,Patacchini R,Maggi CA,Novellino E,Rovero P

    更新日期:2002-12-01 00:00:00

  • Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity.

    abstract::Searching for new substances with antileishmanial activity, we synthesized and evaluated a series of α,α-difluorohydrazide and α,α-difluoramides against Leishmania amazonensis arginase (LaArg). Four α,α-difluorohydrazide derivatives showed activity against LaArg with Ki in the range of 1.3-26 μM. The study of the kine...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.07.022

    authors: Crizanto de Lima E,Castelo-Branco FS,Maquiaveli CC,Farias AB,Rennó MN,Boechat N,Silva ER

    更新日期:2019-09-01 00:00:00

  • A prenylbisabolane with NF-kappaB inhibiting properties from Cascarilla (Croton eluteria).

    abstract::Investigation of the bark of Croton eluteria Bennett for biologically active compounds has led to the isolation of the new prenylbisabolane 3, whose structure was assessed by spectroscopic methods. The corresponding known enone 4 and the eudesmane sesquiterpene 2 were also obtained. Compound 3 proved active in selecti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.04.025

    authors: Campagnuolo C,Fattorusso E,Petrucci F,Taglialatela-Scafati O,Appendino G,Marquez N,Muñoz E

    更新日期:2005-07-01 00:00:00

  • Anti-inflammatory profile of some synthesized heterocyclic pyridone and pyridine derivatives fused with steroidal structure.

    abstract::We herein report the anti-inflammatory activity of some newly synthesized heterocyclic pyridone and pyridine derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All compounds, except 3b, 22, and 23, were interestingly less toxic t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.02.045

    authors: Amr AG,Abdulla MM

    更新日期:2006-07-01 00:00:00

  • Conformationally locked thiosugars as potent alpha-mannosidase inhibitors: synthesis, biochemical and docking studies.

    abstract::A series of thiosugar derivatives (thiolevomannosans) derived from mannose were synthesized and their inhibitory activity was tested against alpha-mannosidase (jack bean). These inhibitors were found to be more potent than the well-known inhibitors like kifunensine and deoxymannojirimycin based on docking and biochemi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.06.011

    authors: Sivapriya K,Hariharaputran S,Suhas VL,Chandra N,Chandrasekaran S

    更新日期:2007-09-01 00:00:00

  • Elaboration of a fragment library hit produces potent and selective aspartate semialdehyde dehydrogenase inhibitors.

    abstract::Aspartate-β-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the aspartate metabolic pathway which leads to the biosynthesis of several essential amino acids and some important metabolites. This pathway is crucial for many metabolic processes in plants and microbes like bacteria and fungi, but is a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.09.017

    authors: Thangavelu B,Bhansali P,Viola RE

    更新日期:2015-10-15 00:00:00

  • Synthesis and photodynamic activity of zinc(II) phthalocyanine derivatives bearing methoxy and trifluoromethylbenzyloxy substituents in homogeneous and biological media.

    abstract::Two zinc(II) phthalocyanines bearing either four methoxy (ZnPc 3) or trifluoromethylbenzyloxy (ZnPc 4) substituents have been synthesized by a two-step procedure starting from 4-nitrophthalonitrile. Absorption and fluorescence spectroscopic studies were analyzed in different media. These compounds are essentially non-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.10.003

    authors: Yslas EI,Rivarola V,Durantini EN

    更新日期:2005-01-03 00:00:00

  • Comparison of the dark and light-induced toxicity of thio and seleno analogues of the thiopyrylium dye AA1.

    abstract::2,6-Bis(4-anilino)-4-(4-N,N-dimethylanilino)thiopyrylium chloride (AA1) and -selenopyrylium chloride (AA1-Se) and 2,6-bis(4-anilino)-4-(4-N-morpholinophenyl)thiopyrylium chloride (1) and -selenopyrylium chloride (2) were prepared via the addition of 4-N,N-dimethylanilino magnesium bromide and 4-N-morpholinophenyl magn...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.03.025

    authors: Detty MR,Gibson SL,Hilf R

    更新日期:2004-05-15 00:00:00

  • Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.

    abstract::This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.07.064

    authors: Evangelista W,Weir RL,Ellingson SR,Harris JB,Kapoor K,Smith JC,Baudry J

    更新日期:2016-10-15 00:00:00

  • An efficient asymmetric synthesis of (S)-atenolol: using hydrolytic kinetic resolution.

    abstract::Enantiomerically pure (S)-atenolol was prepared by using (R,R) salen Co(III) complex for the resolution of terminal epoxide. This process was carried out at room temperature in excellent enantio selectivity. The method can be applied for large-scale preparation of (S)-atenolol without any problem. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.10.057

    authors: Bose DS,Venkat Narsaiah A

    更新日期:2005-02-01 00:00:00

  • Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New design with improved properties.

    abstract::6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), a key enzyme in the folate biosynthetic pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin. The enzyme is essential for microorganisms, is absent from humans, and is not the target for any existing antibiotics. Theref...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.11.032

    authors: Shi G,Shaw G,Liang YH,Subburaman P,Li Y,Wu Y,Yan H,Ji X

    更新日期:2012-01-01 00:00:00

  • 'Carba'-carfentanil (trans isomer): a μ opioid receptor (MOR) partial agonist with a distinct binding mode.

    abstract::There is strong evidence to indicate that a positively charged nitrogen of endogenous and exogenous opioid ligands forms a salt bridge with the Asp residue in the third transmembrane helix of opioid receptors. To further examine the role of this electrostatic interaction in opioid receptor binding and activation, we s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.07.033

    authors: Weltrowska G,Lemieux C,Chung NN,Guo JJ,Wilkes BC,Schiller PW

    更新日期:2014-09-01 00:00:00

  • Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity.

    abstract::Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (±)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (±)-stepholidine, were synthesized and evaluated for affinity at dopamine and σ receptors in order to evaluate effects on...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.03.037

    authors: Gadhiya S,Madapa S,Kurtzman T,Alberts IL,Ramsey S,Pillarsetty NK,Kalidindi T,Harding WW

    更新日期:2016-05-01 00:00:00

  • Design, synthesis, and activity of caffeoyl pyrrolidine derivatives as potential gelatinase inhibitors.

    abstract::The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure-activity relationship results from these tested compou...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.07.025

    authors: Li YL,Xu WF

    更新日期:2004-10-01 00:00:00

  • Synthesis and evaluation of 18F labeled crizotinib derivative [18F]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor.

    abstract::c-MET-positive NSCLC is an important subtype accounting for about 5%~22% of lung cancer. NSCLC patients with activating c-MET are intensively sensitive to c-MET selective receptor tyrosine kinase (RTK) inhibitors, so we aimed to develop a specific PET probe targeting to c-MET-positive NSCLC for potential patients scre...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115577

    authors: Lin Q,Zhang Y,Fu Z,Hu B,Si Z,Zhao Y,Shi H,Cheng D

    更新日期:2020-08-01 00:00:00

  • Modification at the C9 position of the marine natural product isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell activity.

    abstract::As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos sponge. This library of ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.08.042

    authors: Gul W,Hammond NL,Yousaf M,Bowling JJ,Schinazi RF,Wirtz SS,de Castro Andrews G,Cuevas C,Hamann MT

    更新日期:2006-12-15 00:00:00

  • Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing 40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice.

    abstract::Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor-bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3-hydroxy-4-(o-car...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.04.010

    authors: Wu H,Micca PL,Makar MS,Miura M

    更新日期:2006-08-01 00:00:00

  • Fancy bioisosteres: synthesis, SAR, and pharmacological investigations of novel nonaromatic dopamine D3 receptor ligands.

    abstract::Structural variations of the lead compound FAUC 88 led to dopaminergic enynes with an extended pi-system when Pd-catalyzed cross coupling reactions were employed for the key reaction steps. The dienyne 9b displayed substantial affinity for the dopamine receptor subtype D3 and remarkable selectivity over D4. Compared t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.04.047

    authors: Lenz C,Boeckler F,Hübner H,Gmeiner P

    更新日期:2005-07-15 00:00:00

  • The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes.

    abstract::The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.08.013

    authors: Hao M,Li Y,Liu L,Yuan X,Gao Y,Guan Z,Li W

    更新日期:2017-10-15 00:00:00

  • Analgesic agents without gastric damage: design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors.

    abstract::In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.10.029

    authors: Zheng X,Oda H,Takamatsu K,Sugimoto Y,Tai A,Akaho E,Ali HI,Oshiki T,Kakuta H,Sasaki K

    更新日期:2007-01-15 00:00:00