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Designing inhibitors of anthrax toxin

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Bibliography

  • Ravina E. The evolution of drug discovery: from traditional medicines to modern drugs. Wiley-VCH, Weinheim, Germany; 2011
  • Krogsgaard-Larsen P, Stromgaard K, Madsen U. Drug design and discovery. CRC Press Taylor & Francis Group, New York, USA; 2010
  • Schneider G, Baringhaus K. Molecular design: concepts and applications. Wiley-VCH, Weinheim, Germany; 2008
  • Bouzianas DG. Medical countermeasures to protect humans from anthrax bioterrorism. Trends Microbiol 2009;17:522-8
  • Chen Z, Moayeri M, Purcell R. Monoclonal antibody therapies against anthrax. Toxins (Basel) 2011;3:1004-19
  • Beierlein JM, Anderson AC. New developments in vaccines, inhibitors of anthrax toxins, and antibiotic therapeutics for bacillus anthracis. Curr Med Chem 2011;18:5083-94
  • Bouzianas DG. Current and future medical approaches to combat the anthrax threat. J Med Chem 2010;53:4305-31
  • Artenstein AW, Opal SM. Novel approaches to the treatment of systemic anthrax. Clin Infect Dis 2012;54:1148-61
  • Fouet A. The surface of bacillus anthracis. Mol Aspects Med 2009;30:374-85
  • Young JA, Collier RJ. Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu Rev Biochem 2007;76:243-65
  • Moayeri M, Leppla SH. Cellular and systemic effects of anthrax lethal toxin and edema toxin. Mol Aspects Med 2009;30:439-55
  • Barth H, Aktories K, Popoff MR, et al. Binary bacterial toxins: biochemistry, biology, and applications of common clostridium and bacillus proteins. Microbiol Mol Biol Rev 2004;68:373-402
  • Petosa C, Collier RJ, Klimpel KR, et al. Crystal structure of the anthrax toxin protective antigen. Nature 1997;385:833-8
  • Kintzer AF, Thoren KL, Sterling HJ, et al. The protective antigen component of anthrax toxin forms functional octameric complexes. J Mol Biol 2009;392:614-29
  • Mogridge J, Cunningham K, Collier RJ. Stoichiometry of anthrax toxin complexes. Biochemistry 2002;41:1079-82
  • Pilpa RM, Bayrhuber M, Marlett JM, et al. A receptor-based switch that regulates anthrax toxin pore formation. PLoS Pathog 2011;7:e1002354
  • Blaustein RO, Koehler TM, Collier RJ, et al. Anthrax toxin: channel-forming activity of protective antigen in planar phospholipid bilayers. Proc Natl Acad Sci USA 1989;86:2209-13
  • Katayama H, Janowiak BE, Brzozowski M, et al. GroEL as a molecular scaffold for structural analysis of the anthrax toxin pore. Nat Struct Mol Biol 2008;15:754-60
  • Zhang S, Udho E, Wu Z, et al. Protein translocation through anthrax toxin channels formed in planar lipid bilayers. Biophys J 2004;87:3842-9
  • Zhang S, Finkelstein A, Collier RJ. Evidence that translocation of anthrax toxin's lethal factor is initiated by entry of its N terminus into the protective antigen channel. Proc Natl Acad Sci USA 2004;101:16756-61
  • Krantz BA, Melnyk RA, Zhang S, et al. A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore. Science 2005;309:777-81
  • Basilio D, Juris SJ, Collier RJ, et al. Evidence for a proton-protein symport mechanism in the anthrax toxin channel. J Gen Physiol 2009;133:307-14
  • Basilio D, Kienker PK, Briggs SW, et al. A kinetic analysis of protein transport through the anthrax toxin channel. J Gen Physiol 2011;137:521-31
  • Basilio D, Jennings-Antipov LD, Jakes KS, et al. Trapping a translocating protein within the anthrax toxin channel: implications for the secondary structure of permeating proteins. J Gen Physiol 2011;137:343-56
  • Janowiak BE, Finkelstein A, Collier RJ. An approach to characterizing single-subunit mutations in multimeric prepores and pores of anthrax protective antigen. Protein Sci 2009;18:348-58
  • Thoren KL, Worden EJ, Yassif JM, et al. Lethal factor unfolding is the most force-dependent step of anthrax toxin translocation. Proc Natl Acad Sci USA 2009;106:21555-60
  • Pentelute BL, Sharma O, Collier RJ. Chemical dissection of protein translocation through the anthrax toxin pore. Angew Chem Int Ed Engl 2011;50:2294-6
  • Feld GK, Brown MJ, Krantz BA. Ratcheting up protein translocation with anthrax toxin. Protein Sci 2012;21:606-24
  • Brown MJ, Thoren KL, Krantz BA. Charge requirements for proton gradient-driven translocation of anthrax toxin. J Biol Chem 2011;286:23189-99
  • Krantz BA, Finkelstein A, Collier RJ. Protein translocation through the anthrax toxin transmembrane pore is driven by a proton gradient. J Mol Biol 2006;355:968-79
  • Duesbery NS, Webb CP, Leppla SH, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 1998;280:734-7
  • Vitale G, Bernardi L, Napolitani G, et al. Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J 2000;352(Pt 3):739-45
  • Levinsohn JL, Newman ZL, Hellmich KA, et al. Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. PLoS Pathog 2012;8:e1002638
  • Leppla SH. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci USA 1982;79:3162-6
  • Dumetz F, Jouvion G, Khun H, et al. Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax. Am J Pathol 2011;178:2523-35
  • Leysath CE, Chen KH, Moayeri M, et al. Mouse monoclonal antibodies to anthrax edema factor protect against infection. Infect Immun 2011;79:4609-16
  • Liu S, Zhang Y, Moayeri M, et al. Key tissue targets responsible for anthrax-toxin-induced lethality. Nature 2013;501:63-8
  • Guarner J, Jernigan JA, Shieh WJ, et al. Pathology and pathogenesis of bioterrorism-related inhalational anthrax. Am J Pathol 2003;163:701-9
  • Nigrovic LE, Thompson KM. The lyme vaccine: a cautionary tale. Epidemiol Infect 2007;135:1-8
  • Jang KH, Nam SJ, Locke JB, et al. Anthracimycin, a potent anthrax antibiotic from a marine-derived actinomycete. Angew Chem Int Ed Engl 2013;52:7822-4
  • Bouzianas DG. Potential biological targets of bacillus anthracis in anti-infective approaches against the threat of bioterrorism. Expert Rev Anti Infect Ther 2007;5:665-84
  • Bartlett JG, Inglesby TV Jr, Borio L. Management of anthrax. Clin Infect Dis 2002;35:851-8
  • Bull JJ, Parrish CR. Microbiology. A binding contract for anthrax. Science 2002;297:201-2
  • Mock M, Fouet A. Anthrax. Annu Rev Microbiol 2001;55:647-71
  • Gilligan PH. Therapeutic challenges posed by bacterial bioterrorism threats. Curr Opin Microbiol 2002;5:489-95
  • Rainey GJ, Young JA. Antitoxins: novel strategies to target agents of bioterrorism. Nat Rev Microbiol 2004;2:721-6
  • Friedlander AM. Tackling anthrax. Nature 2001;414:160-1
  • Fox JL. Anthrax drug first antibacterial mAb to win approval. Nat Biotechnol 2013;31:8
  • Russell L, Pedersen M, Jensen AV, et al. Two anthrax cases with soft tissue infection, severe oedema and sepsis in danish heroin users. BMC Infect Dis 2013;13:408
  • Bradley KA, Mogridge J, Mourez M, et al. Identification of the cellular receptor for anthrax toxin. Nature 2001;414:225-9
  • Scobie HM, Rainey GJ, Bradley KA, et al. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci USA 2003;100:5170-4
  • Martchenko M, Jeong SY, Cohen SN. Heterodimeric integrin complexes containing beta1-integrin promote internalization and lethality of anthrax toxin. Proc Natl Acad Sci USA 2010;107:15583-8
  • Little SF, Leppla SH, Cora E. Production and characterization of monoclonal antibodies to the protective antigen component of bacillus anthracis toxin. Infect Immun 1988;56:1807-13
  • Bann JG, Cegelski L, Hultgren SJ. LRP6 holds the key to the entry of anthrax toxin. Cell 2006;124:1119-21
  • Basha S, Rai P, Poon V, et al. Polyvalent inhibitors of anthrax toxin that target host receptors. Proc Natl Acad Sci USA 2006;103:13509-13
  • Cai C, Che J, Xu L, et al. Tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors. PLoS One 2011;6:e20646
  • Rogers MS, Cryan LM, Habeshian KA, et al. A FRET-based high throughput screening assay to identify inhibitors of anthrax protective antigen binding to capillary morphogenesis gene 2 protein. PLoS One 2012;7:e39911
  • Cryan LM, Habeshian KA, Caldwell TP, et al. Identification of small molecules that inhibit the interaction of TEM8 with anthrax protective antigen using a FRET assay. J Biomol Screen 2013;18:714-25
  • Cryan LM, Rogers MS. Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy. Front Biosci (Landmark Ed) 2011;16:1574-88
  • Sarac MS, Peinado JR, Leppla SH, et al. Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo. Infect Immun 2004;72:602-5
  • Kacprzak MM, Peinado JR, Than ME, et al. Inhibition of furin by polyarginine-containing peptides: nanomolar inhibition by nona-D-arginine. J Biol Chem 2004;279:36788-94
  • Tonello F, Seveso M, Marin O, et al. Screening inhibitors of anthrax lethal factor. Nature 2002;418:386
  • Turk BE, Wong TY, Schwarzenbacher R, et al. The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor. Nat Struct Mol Biol 2004;11:60-6
  • Peinado JR, Kacprzak MM, Leppla SH, et al. Cross-inhibition between furin and lethal factor inhibitors. Biochem Biophys Res Commun 2004;321:601-5
  • Shiryaev SA, Remacle AG, Ratnikov BI, et al. Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens. J Biol Chem 2007;282:20847-53
  • Remacle AG, Gawlik K, Golubkov VS, et al. Selective and potent furin inhibitors protect cells from anthrax without significant toxicity. Int J Biochem Cell Biol 2010;42:987-95
  • Opal SM, Artenstein AW, Cristofaro PA, et al. Inter-alpha-inhibitor proteins are endogenous furin inhibitors and provide protection against experimental anthrax intoxication. Infect Immun 2005;73:5101-5
  • Opal SM, Lim YP, Cristofaro P, et al. Inter-alpha inhibitor proteins: a novel therapeutic strategy for experimental anthrax infection. Shock 2011;35:42-4
  • Worachartcheewan A, Nantasenamat C, Naenna T, et al. Modeling the activity of furin inhibitors using artificial neural network. Eur J Med Chem 2009;44:1664-73
  • Moayeri M, Wiggins JF, Lindeman RE, et al. Cisplatin inhibition of anthrax lethal toxin. Antimicrob Agents Chemother 2006;50:2658-65
  • Rubert Perez C, Lopez-Perez D, Chmielewski J, et al. Small molecule inhibitors of anthrax toxin-induced cytotoxicity targeted against protective antigen. Chem Biol Drug Des 2012;79:260-9
  • Wein AN, Williams BN, Liu S, et al. Small molecule inhibitors of bacillus anthracis protective antigen proteolytic activation and oligomerization. J Med Chem 2012;55:7998-8006
  • Mourez M, Kane RS, Mogridge J, et al. Designing a polyvalent inhibitor of anthrax toxin. Nat Biotechnol 2001;19:958-61
  • Gujraty K, Sadacharan S, Frost M, et al. Functional characterization of peptide-based anthrax toxin inhibitors. Mol Pharm 2005;2:367-72
  • Rai P, Padala C, Poon V, et al. Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins. Nat Biotechnol 2006;24:582-6
  • Gujraty KV, Joshi A, Saraph A, et al. Synthesis of polyvalent inhibitors of controlled molecular weight: structure-activity relationship for inhibitors of anthrax toxin. Biomacromolecules 2006;7:2082-5
  • Gujraty KV, Yanjarappa MJ, Saraph A, et al. Synthesis of homopolymers and copolymers containing an active ester of acrylic acid by RAFT: scaffolds for controlling polyvalent ligand display. J Polym Sci A Polym Chem 2008;46:7246-57
  • Rai PR, Saraph A, Ashton R, et al. Raftlike polyvalent inhibitors of the anthrax toxin: modulating inhibitory potency by formation of lipid microdomains. Angew Chem Int Ed Engl 2007;46:2207-9
  • Vance D, Shah M, Joshi A, et al. Polyvalency: a promising strategy for drug design. Biotechnol Bioeng 2008;101:429-34
  • Joshi A, Kate S, Poon V, et al. Structure-based design of a heptavalent anthrax toxin inhibitor. Biomacromolecules 2011;12:791-6
  • Karginov VA, Nestorovich EM, Moayeri M, et al. Blocking anthrax lethal toxin at the protective antigen channel by using structure-inspired drug design. Proc Natl Acad Sci USA 2005;102:15075-80
  • Abrami L, Kunz B, van der Goot FG. Anthrax toxin triggers the activation of src-like kinases to mediate its own uptake. Proc Natl Acad Sci USA 2010;107:1420-4
  • Abrami L, Bischofberger M, Kunz B, et al. Endocytosis of the anthrax toxin is mediated by clathrin, actin and unconventional adaptors. PLoS Pathog 2010;6:e1000792
  • Jeong SY, Martchenko M, Cohen SN. Calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis. Proc Natl Acad Sci USA 2013;110:E4007-15
  • Gillespie EJ, Ho CL, Balaji K, et al. Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses. Proc Natl Acad Sci USA 2013;110:E4904-12
  • Bann JG. Anthrax toxin protective antigen–insights into molecular switching from prepore to pore. Protein Sci 2012;21:1-12
  • Zhu PJ, Hobson JP, Southall N, et al. Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death. Bioorg Med Chem 2009;17:5139-45
  • Hobson JP, Liu S, Rono B, et al. Imaging specific cell-surface proteolytic activity in single living cells. Nat Methods 2006;3:259-61
  • Rosenfeld R, Marcus H, Ben-Arie E, et al. Isolation and chimerization of a highly neutralizing antibody conferring passive protection against lethal bacillus anthracis infection. PLoS One 2009;4:e6351
  • Mechaly A, Levy H, Epstein E, et al. A novel mechanism for antibody-based anthrax toxin neutralization: inhibition of prepore-to-pore conversion. J Biol Chem 2012;287:32665-73
  • Collier RJ. Membrane translocation by anthrax toxin. Mol Aspects Med 2009;30:413-22
  • Thoren KL, Krantz BA. The unfolding story of anthrax toxin translocation. Mol Microbiol 2011;80:588-95
  • Nablo BJ, Panchal RG, Bavari S, et al. Anthrax toxin-induced rupture of artificial lipid bilayer membranes. J Chem Phys 2013;139:065101
  • Sellman BR, Mourez M, Collier RJ. Dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax. Science 2001;292:695-7
  • Singh Y, Khanna H, Chopra AP, et al. A dominant negative mutant of bacillus anthracis protective antigen inhibits anthrax toxin action in vivo. J Biol Chem 2001;276:22090-4
  • Yan M, Collier RJ. Characterization of dominant-negative forms of anthrax protective antigen. Mol Med 2003;9:46-51
  • Cao S, Guo A, Liu Z, et al. Investigation of new dominant-negative inhibitors of anthrax protective antigen mutants for use in therapy and vaccination. Infect Immun 2009;77:4679-87
  • Aulinger BA, Roehrl MH, Mekalanos JJ, et al. Combining anthrax vaccine and therapy: a dominant-negative inhibitor of anthrax toxin is also a potent and safe immunogen for vaccines. Infect Immun 2005;73:3408-14
  • Janowiak BE, Fischer A, Collier RJ. Effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigen. J Biol Chem 2010;285:8130-7
  • Sun J, Lang AE, Aktories K, et al. Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocation. Proc Natl Acad Sci USA 2008;105:4346-51
  • Montal M, Mueller P. Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proc Natl Acad Sci USA 1972;69:3561-6
  • Nestorovich EM, Bezrukov SM. Obstructing toxin pathways by targeted pore blockage. Chem Rev 2012;112(12):6388-430
  • Blaustein RO, Finkelstein A. Diffusion limitation in the block by symmetric tetraalkylammonium ions of anthrax toxin channels in planar phospholipid bilayer membranes. J Gen Physiol 1990;96:943-57
  • Blaustein RO, Finkelstein A. Voltage-dependent block of anthrax toxin channels in planar phospholipid bilayer membranes by symmetric tetraalkylammonium ions. Effects on macroscopic conductance. J Gen Physiol 1990;96:905-19
  • Blaustein RO, Lea EJ, Finkelstein A. Voltage-dependent block of anthrax toxin channels in planar phospholipid bilayer membranes by symmetric tetraalkylammonium ions. Single-channel analysis. J Gen Physiol 1990;96:921-42
  • Orlik F, Schiffler B, Benz R. Anthrax toxin protective antigen: inhibition of channel function by chloroquine and related compounds and study of binding kinetics using the current noise analysis. Biophys J 2005;88:1715-24
  • Beitzinger C, Bronnhuber A, Duscha K, et al. Designed azolopyridinium salts block protective antigen pores in vitro and protect cells from anthrax toxin. PLoS One 2013;8:e66099
  • Karginov VA. Cyclodextrin derivatives as anti-infectives. Curr Opin Pharmacol 2013;13:717-25
  • Karginov VA, Nestorovich EM, Yohannes A, et al. Search for cyclodextrin-based inhibitors of anthrax toxins: synthesis, structural features, and relative activities. Antimicrob Agents Chemother 2006;50:3740-53
  • Diaz-Moscoso A, Mendez-Ardoy A, Ortega-Caballero F, et al. Symmetry complementarity-guided design of anthrax toxin inhibitors based on beta-cyclodextrin: synthesis and relative activities of face-selective functionalized polycationic clusters. ChemMedChem 2011;6:181-92
  • Yannakopoulou K, Jicsinszky L, Aggelidou C, et al. Symmetry requirements for effective blocking of pore-forming toxins: comparative study with alpha-, beta-, and gamma-cyclodextrin derivatives. Antimicrob Agents Chemother 2011;55:3594-7
  • Moayeri M, Robinson TM, Leppla SH, et al. In vivo efficacy of beta-cyclodextrin derivatives against anthrax lethal toxin. Antimicrob Agents Chemother 2008;52:2239-41
  • Dietrich PS, McGivern JG, Delgado SG, et al. Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia. J Neurochem 1998;70:2262-72
  • Catterall WA, Perez-Reyes E, Snutch TP, et al. International union of pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 2005;57:411-25
  • Nestorovich EM, Karginov VA, Popoff MR, et al. Tailored ss-cyclodextrin blocks the translocation pores of binary exotoxins from C. botulinum and C. perfringens and protects cells from intoxication. PLoS One 2011;6:e23927
  • Bezrukov SM, Liu X, Karginov VA, et al. Interactions of high-affinity cationic blockers with the translocation pores of B. anthracis, C. botulinum, and C. perfringens binary toxins. Biophys J 2012;103:1208-17
  • Friedlander AM. Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. J Biol Chem 1986;261:7123-6
  • Gordon VM, Leppla SH, Hewlett EL. Inhibitors of receptor-mediated endocytosis block the entry of bacillus anthracis adenylate cyclase toxin but not that of bordetella pertussis adenylate cyclase toxin. Infect Immun 1988;56:1066-9
  • Finkelstein A. The channel formed in planar lipid bilayers by the protective antigen component of anthrax toxin. Toxicology 1994;87:29-41
  • Dal Molin F, Tonello F, Ladant D, et al. Cell entry and cAMP imaging of anthrax edema toxin. EMBO J 2006;25:5405-13
  • Artenstein AW, Opal SM, Cristofaro P, et al. Chloroquine enhances survival in bacillus anthracis intoxication. J Infect Dis 2004;190:1655-60
  • Sanchez AM, Thomas D, Gillespie EJ, et al. Amiodarone and bepridil inhibit anthrax toxin entry into host cells. Antimicrob Agents Chemother 2007;51:2403-11
  • Backer MV, Patel V, Jehning BT, et al. Inhibition of anthrax protective antigen outside and inside the cell. Antimicrob Agents Chemother 2007;51:245-51
  • Moayeri M, Crown D, Jiao GS, et al. Small-molecule inhibitors of lethal factor protease activity protect against anthrax infection. Antimicrob Agents Chemother 2013;57:4139-45
  • Abrami L, Brandi L, Moayeri M, et al. Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin. Cell Rep 2013;5(4):986-96
  • Montecucco C, Tonello F, Zanotti G. Stop the killer: how to inhibit the anthrax lethal factor metalloprotease. Trends Biochem Sci 2004;29:282-5
  • Dalkas GA, Papakyriakou A, Vlamis-Gardikas A, et al. Low molecular weight inhibitors of the protease anthrax lethal factor. Mini Rev Med Chem 2008;8:290-306
  • Turk BE. Discovery and development of anthrax lethal factor metalloproteinase inhibitors. Curr Pharm Biotechnol 2008;9:24-33
  • Tonello F, Montecucco C. The anthrax lethal factor and its MAPK kinase-specific metalloprotease activity. Mol Aspects Med 2009;30:431-8
  • Panchal RG, Hermone AR, Nguyen TL, et al. Identification of small molecule inhibitors of anthrax lethal factor. Nat Struct Mol Biol 2004;11:67-72
  • Shoop WL, Xiong Y, Wiltsie J, et al. Anthrax lethal factor inhibition. Proc Natl Acad Sci USA 2005;102:7958-63
  • Goldman ME, Cregar L, Nguyen D, et al. Cationic polyamines inhibit anthrax lethal factor protease. BMC Pharmacol 2006;6:8
  • Kuzmic P, Cregar L, Millis SZ, et al. Mixed-type noncompetitive inhibition of anthrax lethal factor protease by aminoglycosides. FEBS J 2006;273:3054-62
  • Fridman M, Belakhov V, Lee LV, et al. Dual effect of synthetic aminoglycosides: antibacterial activity against bacillus anthracis and inhibition of anthrax lethal factor. Angew Chem Int Ed Engl 2005;44:447-52
  • Kim C, Gajendran N, Mittrucker HW, et al. Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc Natl Acad Sci USA 2005;102:4830-5
  • Wang W, Mulakala C, Ward SC, et al. Retrocyclins kill bacilli and germinating spores of bacillus anthracis and inactivate anthrax lethal toxin. J Biol Chem 2006;281:32755-64
  • Wickliffe KE, Leppla SH, Moayeri M. Killing of macrophages by anthrax lethal toxin: involvement of the N-end rule pathway. Cell Microbiol 2008;10:1352-62
  • Chiu TL, Amin EA. Development of a comprehensive, validated pharmacophore hypothesis for anthrax toxin lethal factor (LF) inhibitors using genetic algorithms, pareto scoring, and structural biology. J Chem Inf Model 2012;52:1886-97
  • Jiao GS, Kim S, Moayeri M, et al. Antidotes to anthrax lethal factor intoxication. Part 1: discovery of potent lethal factor inhibitors with in vivo efficacy. Bioorg Med Chem Lett 2010;20:6850-3
  • Kim S, Jiao GS, Moayeri M, et al. Antidotes to anthrax lethal factor intoxication. Part 2: structural modifications leading to improved in vivo efficacy. Bioorg Med Chem Lett 2011;21:2030-3
  • Jiao GS, Kim S, Moayeri M, et al. Antidotes to anthrax lethal factor intoxication. Part 3: evaluation of core structures and further modifications to the C2-side chain. Bioorg Med Chem Lett 2012;22:2242-6
  • Sirard JC, Mock M, Fouet A. The three bacillus anthracis toxin genes are coordinately regulated by bicarbonate and temperature. J Bacteriol 1994;176:5188-92
  • Mabry R, Brasky K, Geiger R, et al. Detection of anthrax toxin in the serum of animals infected with bacillus anthracis by using engineered immunoassays. Clin Vaccine Immunol 2006;13:671-7
  • Molin FD, Fasanella A, Simonato M, et al. Ratio of lethal and edema factors in rabbit systemic anthrax. Toxicon 2008;52:824-8
  • Laine E, Martinez L, Ladant D, et al. Molecular motions as a drug target: mechanistic simulations of anthrax toxin edema factor function led to the discovery of novel allosteric inhibitors. Toxins (Basel) 2012;4:580-604
  • Schein CH, Chen D, Ma L, et al. Pharmacophore selection and redesign of non-nucleotide inhibitors of anthrax edema factor. Toxins (Basel) 2012;4:1288-300
  • Seifert R, Dove S. Inhibitors of bacillus anthracis edema factor. Pharmacol Ther 2013;140:200-12
  • Chen Z, Moayeri M, Zhao H, et al. Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding. Proc Natl Acad Sci USA 2009;106:13487-92
  • Winterroth L, Rivera J, Nakouzi AS, et al. Neutralizing monoclonal antibody to edema toxin and its effect on murine anthrax. Infect Immun 2010;78:2890-8
  • Makiya M, Dolan M, Agulto L, et al. Structural basis of anthrax edema factor neutralization by a neutralizing antibody. Biochem Biophys Res Commun 2012;417:324-9
  • Soelaiman S, Wei BQ, Bergson P, et al. Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough. J Biol Chem 2003;278:25990-7
  • Chen D, Misra M, Sower L, et al. Novel inhibitors of anthrax edema factor. Bioorg Med Chem 2008;16:7225-33
  • Laine E, Goncalves C, Karst JC, et al. Use of allostery to identify inhibitors of calmodulin-induced activation of bacillus anthracis edema factor. Proc Natl Acad Sci USA 2010;107:11277-82
  • Taha HM, Schmidt J, Gottle M, et al. Molecular analysis of the interaction of anthrax adenylyl cyclase toxin, edema factor, with 2'(3')-O-(N-(methyl)anthraniloyl)-substituted purine and pyrimidine nucleotides. Mol Pharmacol 2009;75:693-703
  • Taha H, Dove S, Geduhn J, et al. Inhibition of the adenylyl cyclase toxin, edema factor, from bacillus anthracis by a series of 18 mono- and bis-(M)ANT-substituted nucleoside 5'-triphosphates. Naunyn Schmiedebergs Arch Pharmacol 2012;385:57-68
  • Shen Y, Zhukovskaya NL, Zimmer MI, et al. Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection. Proc Natl Acad Sci USA 2004;101:3242-7
  • Suryanarayana S, Wang JL, Richter M, et al. Distinct interactions of 2'- and 3'-O-(N-methyl)anthraniloyl-isomers of ATP and GTP with the adenylyl cyclase toxin of bacillus anthracis, edema factor. Biochem Pharmacol 2009;78:224-30
  • Pinto C, Lushington GH, Richter M, et al. Structure-activity relationships for the interactions of 2'- and 3'-(O)-(N-methyl)anthraniloyl-substituted purine and pyrimidine nucleotides with mammalian adenylyl cyclases. Biochem Pharmacol 2011;82:358-70
  • Chen D, Ma L, Kanalas JJ, et al. Structure-based redesign of an edema toxin inhibitor. Bioorg Med Chem 2012;20:368-76
  • Dolgin E. Animal rule for drug approval creates a jungle of confusion. Nat Med 2013;19:118-19
  • Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997;23:3-25
  • Nestorovich EM, Karginov VA, Berezhkovskii AM, et al. Blockage of anthrax PA63 pore by a multicharged high-affinity toxin inhibitor. Biophys J 2010;99:134-43

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