JANDA LAB

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DETECTION OF & PROTECTION FROM WARFARE AGENTS

Lin L, Patel EN, Nielsen AL, Turner LD, Tepp WH, Nguyen K, Pellett S, Janda K. Transformation of a metal chelate into a “catch and anchor” inhibitor of Botulinum A protease. Int J Mol Sci. 2023;24(5). PMID: 36901734.

Patel EN, Turner LD, Hixon MS, Janda KD. Identification of slow-binding inhibitors of the BoNT/A protease. ACS Med Chem Lett. 2022;13(4):742-7. PMID: 35450355.

Patel EN, Lin L, Sneller MM, Eubanks LM, Tepp WH, Pellett S, Janda KD. Investigation of salicylanilides as botulinum toxin antagonists. ACS Infect Dis. 2022;8(8):1637-45. PMID: 35877209.

Lin L, Turner LD, Silhar P, Pellett S, Johnson EA, Janda KD. Identification of 3-hydroxy-1,2-dimethylpyridine-4(1H)-thione as a metal-binding motif for the inhibition of botulinum neurotoxin A. RSC Med Chem. 2021;12(1):137-43. PMID: 34046606.

Turner LD, Nielsen AL, Lin L, Pellett S, Sugane T, Olson ME, Johnson EA, Janda KD. Irreversible inhibition of BoNT/A protease: Proximity-driven reactivity contingent upon a bifunctional approach. RSC Med Chem. 2021;12(6):960-9. PMID: 34223161.

Turner LD, Nielsen AL, Lin L, Campedelli AJ, Silvaggi NR, Chen JS, Wakefield AE, Allen KN, Janda KD. Use of crystallography and molecular modeling for the inhibition of the botulinum neurotoxin A protease. ACS Med Chem Lett. 2021;12(8):1318-24. PMID: 34413962.

Lin L, Olson ME, Sugane T, Turner LD, Tararina MA, Nielsen AL, Kurbanov EK, Pellett S, Johnson EA, Cohen SM, Allen KN, Janda KD. Catch and anchor approach to combat both toxicity and longevity of botulinum toxin A. J Med Chem. 2020;63(19):11100-20. PMID: 32886509.

Lin L, Olson ME, Eubanks LM, Janda KD. Strategies to counteract botulinum neurotoxin A: Nature's deadliest biomolecule. Acc Chem Res. 2019;52(8):2322-31. PMID: 31322847.

Bremer PT, Pellett S, Carolan JP, Tepp WH, Eubanks LM, Allen KN, Johnson EA, Janda KD. Metal ions effectively ablate the action of botulinum neurotoxin A. J Am Chem Soc. 2017;139(21):7264-72. PMID: 28475321.

Bremer PT, Adler M, Phung CH, Singh AK, Janda KD. Newly designed quinolinol inhibitors mitigate the effects of botulinum neurotoxin A in enzymatic, cell-based, and ex vivo assays. J Med Chem. 2017;60(1):338-48. PMID: 27966961.

Xue S, Seki H, Remes M, Silhar P, Janda K. Examination of alpha-exosite inhibitors against Botulinum neurotoxin A protease through structure-activity relationship studies of chicoric acid. Bioorg Med Chem Lett. 2017;27(22):4956-9. PMID: 29050781.

Bremer PT, Xue S, Janda KD. Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain. Chem Commun (Camb). 2016;52(84):12521-4. PMID: 27722252.


Harris TL, Wenthur CJ, Diego-Taboada A, Mackenzie G, Corbitt TS, Janda KD. Lycopodium clavatum exine microcapsules enable safe oral delivery of 3,4-diaminopyridine for treatment of botulinum neurotoxin A intoxication. Chem Commun (Camb). 2016;52(22):4187-90. PMID: 26906286.

Seki H, Xue S, Pellett S, Silhar P, Johnson EA, Janda KD. Cellular protection of SNAP-25 against botulinum neurotoxin/A: Inhibition of thioredoxin reductase through a suicide substrate mechanism. J Am Chem Soc. 2016;138(17):5568-75. PMID: 27070533.

Seki H, Xue S, Hixon MS, Pellett S, Remes M, Johnson EA, Janda KD. Toward the discovery of dual inhibitors for botulinum neurotoxin A: Concomitant targeting of endocytosis and light chain protease activity. Chem Commun (Camb). 2015;51(28):6226-9. PMID: 25759983.

Bremer PT, Hixon MS, Janda KD. Benzoquinones as inhibitors of botulinum neurotoxin serotype A. Bioorg Med Chem. 2014;22(15):3971-81. PMID: 24984937.

Harris TL, Lowery CA, Hixon MS, Janda KD. A platform stratifying a sequestering agent and a pharmacological antagonist as a means to negate botulinum neurotoxicity. ACS Chem Neurosci. 2014;5(8):632-6. PMID: 25000171.

Seki H, Pellett S, Silhar P, Stowe GN, Blanco B, Lardy MA, Johnson EA, Janda KD. Synthesis/biological evaluation of hydroxamic acids and their prodrugs as inhibitors for Botulinum neurotoxin A light chain. Bioorg Med Chem. 2014;22(3):1208-17. PMID: 24360826.

Xue S, Javor S, Hixon MS, Janda KD. Probing BoNT/A protease exosites: Implications for inhibitor design and light chain longevity. Biochemistry. 2014;53(43):6820-4. PMID: 25295706.

Lowery CA, Adler M, Borrell A, Janda KD. Scorpion toxins for the reversal of BoNT-induced paralysis. Bioorg Med Chem Lett. 2013;23(24):6743-6. PMID: 24252544.

Silhar P, Silvaggi NR, Pellett S, Capkova K, Johnson EA, Allen KN, Janda KD. Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: Synthesis, crystallography, modeling, kinetic and cellular based studies. Bioorg Med Chem. 2013;21(5):1344-8. PMID: 23340139.

Silhar P, Lardy MA, Hixon MS, Shoemaker CB, Barbieri JT, Struss AK, Lively JM, Javor S, Janda KD. The C-terminus of botulinum A protease has profound and unanticipated kinetic consequences upon the catalytic cleft. ACS Med Chem Lett. 2013;4(2):283-7. PMID: 23565325.

Silhar P, Eubanks LM, Seki H, Pellett S, Javor S, Tepp WH, Johnson EA, Janda KD. Targeting botulinum A cellular toxicity: A prodrug approach. J Med Chem. 2013;56(20):7870-9. PMID: 24127873.

Pier CL, Chen C, Tepp WH, Lin G, Janda KD, Barbieri JT, Pellett S, Johnson EA. Botulinum neurotoxin subtype A2 enters neuronal cells faster than subtype A1. FEBS Lett. 2011;585(1):199-206. PMID: 21126520.

Salzameda NT, Eubanks LM, Zakhari JS, Tsuchikama K, DeNunzio NJ, Allen KN, Hixon MS, Janda KD. A cross-over inhibitor of the botulinum neurotoxin light chain B: A natural product implicating an exosite mechanism of action. Chem Commun (Camb). 2011;47(6):1713-5. PMID: 21203627.

Zakhari JS, Kinoyama I, Struss AK, Pullanikat P, Lowery CA, Lardy M, Janda KD. Synthesis and molecular modeling provide insight into a Pseudomonas aeruginosa quorum sensing conundrum. J Am Chem Soc. 2011;133(11):3840-2. PMID: 21348514.

Zakhari JS, Kinoyama I, Hixon MS, Di Mola A, Globisch D, Janda KD. Formulating a new basis for the treatment against botulinum neurotoxin intoxication: 3,4-diaminopyridine prodrug design and characterization. Bioorg Med Chem. 2011;19(21):6203-9. PMID: 21975066.

Capkova K, Hixon MS, Pellett S, Barbieri JT, Johnson EA, Janda KD. Benzylidene cyclopentenediones: First irreversible inhibitors against botulinum neurotoxin A's zinc endopeptidase. Bioorg Med Chem Lett. 2010;20(1):206-8. PMID: 19914829.

Eubanks LM, Silhar P, Salzameda NT, Zakhari JS, Xiaochuan F, Barbieri JT, Shoemaker CB, Hixon MS, Janda KD. Identification of a natural product antagonist against the botulinum neurotoxin light chain protease. ACS Med Chem Lett. 2010;1(6):268-72. PMID: 20959871.

Mayorov AV, Willis B, Di Mola A, Adler D, Borgia J, Jackson O, Wang J, Luo Y, Tang L, Knapp RJ, Natarajan C, Goodnough MC, Zilberberg N, Simpson LL, Janda KD. Symptomatic relief of botulinum neurotoxin/A intoxication with aminopyridines: A new twist on an old molecule. ACS Chem Biol. 2010;5(12):1183-91. PMID: 20936877.

Nakai Y, Pellett S, Tepp WH, Johnson EA, Janda KD. Toosendanin: Synthesis of the AB-ring and investigations of its anti-botulinum properties (Part II). Bioorg Med Chem. 2010;18(3):1280-7. PMID: 20044261.

Silhar P, Capkova K, Salzameda NT, Barbieri JT, Hixon MS, Janda KD. Botulinum neurotoxin A protease: Discovery of natural product exosite inhibitors. J Am Chem Soc. 2010;132(9):2868-9. PMID: 20158239.

Stowe GN, Silhar P, Hixon MS, Silvaggi NR, Allen KN, Moe ST, Jacobson AR, Barbieri JT, Janda KD. Chirality holds the key for potent inhibition of the botulinum neurotoxin serotype a protease. Org Lett. 2010;12(4):756-9. PMID: 20092262.

Thyagarajan B, Potian JG, Garcia CC, Hognason K, Capkova K, Moe ST, Jacobson AR, Janda KD, McArdle JJ. Effects of hydroxamate metalloendoprotease inhibitors on botulinum neurotoxin A poisoned mouse neuromuscular junctions. Neuropharmacology. 2010;58(8):1189-98. PMID: 20211192.

Capkova K, Salzameda NT, Janda KD. Investigations into small molecule non-peptidic inhibitors of the botulinum neurotoxins. Toxicon. 2009;54(5):575-82. PMID: 19327377.

Fischer A, Nakai Y, Eubanks LM, Clancy CM, Tepp WH, Pellett S, Dickerson TJ, Johnson EA, Janda KD, Montal M. Bimodal modulation of the botulinum neurotoxin protein-conducting channel. Proc Natl Acad Sci U S A. 2009;106(5):1330-5. PMID: 19164566.

Nakai Y, Tepp WH, Dickerson TJ, Johnson EA, Janda KD. Function-oriented synthesis applied to the anti-botulinum natural product toosendanin. Bioorg Med Chem. 2009;17(3):1152-7. PMID: 19131252.

Pires-Alves M, Ho M, Aberle KK, Janda KD, Wilson BA. Tandem fluorescent proteins as enhanced FRET-based substrates for botulinum neurotoxin activity. Toxicon. 2009;53(4):392-9. PMID: 19168088.

Salzameda NT, Barbieri JT, Janda KD. Synthetic substrate for application in both high and low throughput assays for botulinum neurotoxin B protease inhibitors. Bioorg Med Chem Lett. 2009;19(20):5848-50. PMID: 19747823.

Zhou H, Zhou B, Pellett S, Johnson EA, Janda KD. Selection and characterization of a human monoclonal neutralizing antibody for Clostridium botulinum neurotoxin serotype B. Bioorg Med Chem Lett. 2009;19(3):662-4. PMID: 19112017.

Capkova K, Hixon MS, McAllister LA, Janda KD. Toward the discovery of potent inhibitors of botulinum neurotoxin A: Development of a robust LC MS based assay operational from low to subnanomolar enzyme concentrations. Chem Commun (Camb). 2008;10.1039/b808305c(30):3525-7. PMID: 18654701.

Willis B, Eubanks LM, Dickerson TJ, Janda KD. The strange case of the botulinum neurotoxin: Using chemistry and biology to modulate the most deadly poison. Angew Chem Int Ed Engl. 2008;47(44):8360-79. PMID: 18844202.

Zarebski LM, Vaughan K, Sidney J, Peters B, Grey H, Janda KD, Casadevall A, Sette A. Analysis of epitope information related to Bacillus anthracis and Clostridium botulinum. Expert Rev Vaccines. 2008;7(1):55-74. PMID: 18251694.

Zhou B, Carney C, Janda KD. Selection and characterization of human antibodies neutralizing Bacillus anthracis toxin. Bioorg Med Chem. 2008;16(4):1903-13. PMID: 18023190.

Zhou B, Pellett S, Tepp WH, Zhou H, Johnson EA, Janda KD. Delineating the susceptibility of botulinum neurotoxins to denaturation through thermal effects. FEBS Lett. 2008;582(10):1526-31. PMID: 18396167.

Capkova K, Yoneda Y, Dickerson TJ, Janda KD. Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors. Bioorg Med Chem Lett. 2007;17(23):6463-6. PMID: 17951059.

Dickerson TJ, McKenzie KM, Hoyt AS, Wood MR, Janda KD, Brenner SB, Lerner RA. Phage escape libraries for checkmate analysis. Proc Natl Acad Sci U S A. 2007;104(31):12703-8. PMID: 17646645.

Eubanks LM, Hixon MS, Jin W, Hong S, Clancy CM, Tepp WH, Baldwin MR, Malizio CJ, Goodnough MC, Barbieri JT, Johnson EA, Boger DL, Dickerson TJ, Janda KD. An in vitro and in vivo disconnect uncovered through high-throughput identification of botulinum neurotoxin A antagonists. Proc Natl Acad Sci U S A. 2007;104(8):2602-7. PMID: 17293454.

Eubanks LM, Dickerson TJ, Janda KD. Technological advancements for the detection of and protection against biological and chemical warfare agents. Chem Soc Rev. 2007;36(3):458-70. PMID: 17325785.

Silvaggi NR, Boldt GE, Hixon MS, Kennedy JP, Tzipori S, Janda KD, Allen KN. Structures of Clostridium botulinum neurotoxin serotype A light chain complexed with small-molecule inhibitors highlight active-site flexibility. Chem Biol. 2007;14(5):533-42. PMID: 17524984.

Steiniger SC, Altobell LJ, 3rd, Zhou B, Janda KD. Selection of human antibodies against cell surface-associated oligomeric anthrax protective antigen. Mol Immunol. 2007;44(10):2749-55. PMID: 17210180.

Boldt GE, Kennedy JP, Hixon MS, McAllister LA, Barbieri JT, Tzipori S, Janda KD. Synthesis, characterization and development of a high-throughput methodology for the discovery of botulinum neurotoxin a inhibitors. J Comb Chem. 2006;8(4):513-21. PMID: 16827563.

Boldt GE, Eubanks LM, Janda KD. Identification of a botulinum neurotoxin A protease inhibitor displaying efficacy in a cellular model. Chem Commun (Camb). 2006;10.1039/b603099h(29):3063-5. PMID: 16855686.

Boldt GE, Kennedy JP, Janda KD. Identification of a potent botulinum neurotoxin a protease inhibitor using in situ lead identification chemistry. Org Lett. 2006;8(8):1729-32. PMID: 16597152.

Dickerson TJ, Janda KD. The use of small molecules to investigate molecular mechanisms and therapeutic targets for treatment of botulinum neurotoxin A intoxication. ACS Chem Biol. 2006;1(6):359-69. PMID: 17163773.

Fu Z, Chen S, Baldwin MR, Boldt GE, Crawford A, Janda KD, Barbieri JT, Kim JJ. Light chain of botulinum neurotoxin serotype A: Structural resolution of a catalytic intermediate. Biochemistry. 2006;45(29):8903-11. PMID: 16846233.

Ma H, Zhou B, Kim Y, Janda KD. A cyclic peptide-polymer probe for the detection of Clostridium botulinum neurotoxin serotype A. Toxicon. 2006;47(8):901-8. PMID: 16730044.

McAllister LA, Hixon MS, Kennedy JP, Dickerson TJ, Janda KD. Superactivation of the botulinum neurotoxin serotype A light chain metalloprotease: A new wrinkle in botulinum neurotoxin. J Am Chem Soc. 2006;128(13):4176-7. PMID: 16568962.

Eubanks LM, Dickerson TJ, Janda KD. Vitamin B2-mediated cellular photoinhibition of botulinum neurotoxin A. FEBS Lett. 2005;579(24):5361-4. PMID: 16198354.

Zhou B, Wirsching P, Janda KD. Human antibodies against spores of the genus Bacillus: A model study for detection of and protection against anthrax and the bioterrorist threat. Proc Natl Acad Sci U S A. 2002;99(8):5241-6. PMID: 11959974.

Ashley JA, Lin CH, Wirsching P, Janda KD. Monitoring chemical warfare agents: A new method for the detection of methylphosphonic acid. Angew Chem Int Ed Engl. 1999;38(12):1793-5. PMID: 29711182.

Lavey BJ, Janda KD. Catalytic antibody mediated hydrolysis of paraoxon. J Org Chem. 1996;61(21):7633-6. PMID: 11667704.






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