Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Review Article

Is Human Paraoxonase 1 the Saviour Against the Persistent Threat of Organophosphorus Nerve Agents?

Author(s): A. R. Satvik Iyengar and Abhay H. Pande*

Volume 26, Issue 7, 2019

Page: [471 - 478] Pages: 8

DOI: 10.2174/0929866526666190403120259

Price: $65

Abstract

Nerve agents have been used extensively in chemical warfare in the past. However, recent use of Novichok agents have reignited the debate on the threat posed by Organophosphorus Nerve Agents (OPNAs). The currently available therapy for OPNA toxicity is only symptomatic and is potentially ineffective in neutralizing OPNAs. Hence, there is a dire need to develop a prophylactic therapy for counteracting OPNA toxicity. In this regard, human paraoxonase 1 has emerged as the enzyme of choice. In this review, we have focussed upon the recent and past events of OPNA use, their mechanism of action and toxicity. Further, we have emphasized upon the potential of enzyme based therapy and the various advances in the development of paraoxonase 1 as a countermeasure for OPNA poisoning. Finally, we have elaborated the shortcomings of paraoxonase 1 and the work that needs to be undertaken in order to develop human paraoxonase 1 as a prophylactic against OPNA poisoning.

Keywords: Organophosphorus nerve agents, novichok agents, acetylcholinesterase, butrylcholinesterase, paraoxonase 1, nerve agent toxicity, prophylactic.

Graphical Abstract
[1]
Costanzi, S.; Machado, J.H.; Mitchell, M. Nerve agents: What they are, how they work, how to counter them. ACS Chem. Neurosci., 2018, 9(5), 873-885. [http://dx.doi.org/10.1021/acschemneuro.8b00148]. [PMID: 29664277].
[2]
Stone, R.U.K. attack puts nerve agent in the spotlight. Science, 2018, 359(6382), 1314-1315. [http://dx.doi.org/10.1126/science.359.6382.1314]. [PMID: 29567684].
[3]
Vale, J.A.; Marrs, T.C.; Maynard, R.L. Novichok: A murderous nerve agent attack in the UK. Clin. Toxicol. (Phila.), 2018, 56(11), 1093-1097. [http://dx.doi.org/10.1080/15563650.2018.1469759]. [PMID: 29757015].
[4]
Balali-Mood, M.; Saber, H. Recent advances in the treatment of organophosphorous poisonings. Iran. J. Med. Sci., 2012, 37(2), 74-91. [PMID: 23115436].
[5]
Benschop, H.P.; De Jong, L.P. Nerve agent stereoisomers: Analysis, isolation and toxicology. Acc. Chem. Res., 1988, 21, 368-374. [http://dx.doi.org/10.1021/ar00154a003].
[6]
Bigley, A.N.; Raushel, F.M. Catalytic mechanisms for phosphotriesterases. Biochim. Biophys. Acta, 2013, 1834(1), 443-453. [http://dx.doi.org/10.1016/j.bbapap.2012.04.004]. [PMID: 22561533].
[7]
Iyengar, A.R.S.; Pande, A.H. Organophosphate-hydrolyzing enzymes as first-line of defence against nerve agent-poisoning: Perspectives and the road ahead. Protein J., 2016, 35(6), 424-439. [http://dx.doi.org/10.1007/s10930-016-9686-6]. [PMID: 27830420].
[8]
Chai, P.R.; Hayes, B.D.; Erickson, T.B.; Boyer, E.W. Novichok agents: A historical, current, and toxicological perspective. Toxicol Commun, 2018, 2(1), 45-48. [http://dx.doi.org/10.1080/24734306.2018.1475151]. [PMID: 30003185].
[9]
Masson, P.; Nachon, F. Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning. J. Neurochem., 2017, 142(Suppl. 2), 26-40. [http://dx.doi.org/10.1111/jnc.14026]. [PMID: 28542985].
[10]
Dolgin, E. Syrian gas attack reinforces need for better anti-sarin drugs. Nat. Med., 2013, 19(10), 1194-1195. [http://dx.doi.org/10.1038/nm1013-1194]. [PMID: 24100968].
[11]
King, A.M.; Aaron, C.K. Organophosphate and carbamate poisoning. Emerg. Med. Clin. North Am., 2015, 33(1), 133-151. [http://dx.doi.org/10.1016/j.emc.2014.09.010]. [PMID: 25455666].
[12]
Manco, G.; Porzio, E.; Suzumoto, Y. Enzymatic detoxification: A sustainable means of degrading toxic organophosphate pesticides and chemical warfare nerve agents. J. Chem. Technol. Biotechnol., 2018, 93, 2064-2082. [http://dx.doi.org/10.1002/jctb.5603].
[13]
Worek, F.; Wille, T.; Koller, M.; Thiermann, H. Toxicology of organophosphorus compounds in view of an increasing terrorist threat. Arch. Toxicol., 2016, 90(9), 2131-2145. [http://dx.doi.org/10.1007/s00204-016-1772-1]. [PMID: 27349770].
[14]
Price, N.C.; Stevens, L. Fundamentals of enzymology: The cell and molecular biology of catalytic proteins, 3rd ed; Oxford University Press: New York, 1999.
[15]
Wiener, S.W.; Hoffman, R.S. Nerve agents: A comprehensive review. J. Intensive Care Med., 2004, 19(1), 22-37. [http://dx.doi.org/10.1177/0885066603258659]. [PMID: 15035752].
[16]
Moshiri, M.; Alizadeh, A.; Balali-Mood, M. Clinical management of organophosphorus nerve agents’ poisonings. In: Basic and clinicaltoxicology of organophosphorus compounds; Balali-Mood, M.; Abdollahi, M., Eds.; Springer-Verlag: Berlin, 2014; pp. 177-212.
[17]
Gill, K.D.; Flora, G.; Pachauri, V.; Flora, S.J. Neurotoxicity of organophosphates and carbamates. In: Anticholinesterase pesticides: Metabolism, neurotoxicity, and epidemiology; Satoh, T.; Gupta, R.C., Eds.; John Wiley & Sons: Hoboken, NJ, 2011; pp. 237-265. [http://dx.doi.org/10.1002/9780470640500.ch18]
[18]
Aracava, Y.; Pereira, E.F.; Akkerman, M.; Adler, M.; Albuquerque, E.X. Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: Comparison with galantamine. J. Pharmacol. Exp. Ther., 2009, 331(3), 1014-1024. [http://dx.doi.org/10.1124/jpet.109.160028]. [PMID: 19741148].
[19]
Masson, P. Evolution of and perspectives on therapeutic approaches to nerve agent poisoning. Toxicol. Lett., 2011, 206(1), 5-13. [http://dx.doi.org/10.1016/j.toxlet.2011.04.006]. [PMID: 21524695].
[20]
Koplovitz, I.; Stewart, J.R. A comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit. Toxicol. Lett., 1994, 70(3), 269-279. [http://dx.doi.org/10.1016/0378-4274(94)90121-X]. [PMID: 8284794].
[21]
Rochu, D.; Chabrière, E.; Masson, P. Human paraoxonase: A promising approach for pre-treatment and therapy of organophosphorus poisoning. Toxicology, 2007, 233(1-3), 47-59. [http://dx.doi.org/10.1016/j.tox.2006.08.037]. [PMID: 17007987].
[22]
Lenz, D.E.; Yeung, D.; Smith, J.R.; Sweeney, R.E.; Lumley, L.A.; Cerasoli, D.M. Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: Mini review. Toxicology, 2007, 233(1-3), 31-39. [http://dx.doi.org/10.1016/j.tox.2006.11.066]. [PMID: 17188793].
[23]
Shih, T.M.; Rowland, T.C.; McDonough, J.H. Anticonvulsants for nerve agent-induced seizures: The influence of the therapeutic dose of atropine. J. Pharmacol. Exp. Ther., 2007, 320(1), 154-161. [http://dx.doi.org/10.1124/jpet.106.111252]. [PMID: 17015638].
[24]
Westfall, T.C.; Westfall, D.P. Neurotransmission: The autonomic and somatic motor nervous systems. In: Goodman and Gilman’s: The pharmacological basis of therapeutics; Brunton, L.; Chabner, B.A.; Knollmann, B.C., Eds.; McGraw Hill Medical Publishing Division: New York, NY, 2011; pp. 137-181.
[25]
Jokanović, M.; Prostran, M. Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds. Curr. Med. Chem., 2009, 16(17), 2177-2188. [http://dx.doi.org/10.2174/092986709788612729]. [PMID: 19519385].
[26]
Doctor, B.P.; Saxena, A. Bioscavengers for the protection of humans against organophosphate toxicity. Chem. Biol. Interact., 2005, 157-158, 167-171. [http://dx.doi.org/10.1016/j.cbi.2005.10.024]. [PMID: 16293236].
[27]
Boyd, C.E.; Boyd, E.M. The acute toxicity of atropine sulfate. Can. Med. Assoc. J., 1961, 85, 1241-1244. [PMID: 13872140].
[28]
Calesnick, B.; Christensen, J.A.; Richter, M. Human toxicity of various oximes. 2-Pyridine aldoxime methyl chloride, its methane sulfonate salt, and 1,1′-trimethylenebis-(4-formylpyridinium chloride). Arch. Environ. Health, 1967, 15(5), 599-608. [http://dx.doi.org/10.1080/00039896.1967.10664975]. [PMID: 6066265].
[29]
Worek, F.; Bäcker, M.; Thiermann, H.; Szinicz, L.; Mast, U.; Klimmek, R.; Eyer, P. Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning. Hum. Exp. Toxicol., 1997, 16(8), 466-472. [http://dx.doi.org/10.1177/096032719701600808]. [PMID: 9292287].
[30]
Buckley, N.A.; Eddleston, M.; Szinicz, L. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst. Rev., 2005, 1(1)CD005085 [PMID: 15654704].
[31]
Soukup, O.; Tobin, G.; Kumar, U.K.; Binder, J.; Proska, J.; Jun, D.; Fusek, J.; Kuca, K. Interaction of nerve agent antidotes with cholinergic systems. Curr. Med. Chem., 2010, 17(16), 1708-1718. [http://dx.doi.org/10.2174/092986710791111260]. [PMID: 20345348].
[32]
Iyer, R.; Iken, B.; Leon, A. Developments in alternative treatments for organophosphate poisoning. Toxicol. Lett., 2015, 233(2), 200-206. [http://dx.doi.org/10.1016/j.toxlet.2015.01.007]. [PMID: 25595305].
[33]
McDonough, J.H.; McMonagle, J.D.; Shih, T.M. Time-dependent reduction in the anticonvulsant effectiveness of diazepam against soman-induced seizures in guinea pigs. Drug Chem. Toxicol., 2010, 33(3), 279-283. [http://dx.doi.org/10.3109/01480540903483417]. [PMID: 20429808].
[34]
Marrs, T.C. The role of diazepam in the treatment of nerve agent poisoning in a civilian population. Toxicol. Rev., 2004, 23(3), 145-157. [http://dx.doi.org/10.2165/00139709-200423030-00002]. [PMID: 15862082].
[35]
Goldsmith, M.; Ashani, Y. Catalytic bioscavengers as countermeasures against organophosphate nerve agents. Chem. Biol. Interact., 2018, 292, 50-64. [http://dx.doi.org/10.1016/j.cbi.2018.07.006]. [PMID: 29990481].
[36]
Cerasoli, D.M.; Griffiths, E.M.; Doctor, B.P.; Saxena, A.; Fedorko, J.M.; Greig, N.H.; Yu, Q.S.; Huang, Y.; Wilgus, H.; Karatzas, C.N.; Koplovitz, I.; Lenz, D.E. In vitro and in vivo characterization of recombinant human butyrylcholinesterase (Protexia) as a potential nerve agent bioscavenger. Chem. Biol. Interact., 2005, 157-158, 363-365. [http://dx.doi.org/10.1016/j.cbi.2005.10.052]. [PMID: 16429486].
[37]
Egelkrout, E.; Hayden, C.; Wales, M.; Walker, J.; Novikov, B.; Grimsley, J.; Howard, J. Production of the bioscavenger butyrylcholinesterase in maize. Mol. Breed., 2017, 37, 1-12. [https://doi.org/10.1007/s11032-017-0731-8].
[38]
Masson, P.; Lockridge, O. Butyrylcholinesterase for protection from organophosphorus poisons: Catalytic complexities and hysteretic behavior. Arch. Biochem. Biophys., 2010, 494(2), 107-120. [http://dx.doi.org/10.1016/j.abb.2009.12.005]. [PMID: 20004171].
[40]
Reed, B.A.; Sabourin, C.L.; Lenz, D.E. Human butyrylcholinesterase efficacy against nerve agent exposure. J. Biochem. Mol. Toxicol., 2017, 31(5), 1-7. [http://dx.doi.org/10.1002/jbt.21886]. [PMID: 28225154].
[41]
Geyer, B.C.; Kannan, L.; Garnaud, P.E.; Broomfield, C.A.; Cadieux, C.L.; Cherni, I.; Hodgins, S.M.; Kasten, S.A.; Kelley, K.; Kilbourne, J.; Oliver, Z.P.; Otto, T.C.; Puffenberger, I.; Reeves, T.E.; Robbins, N.I.I.; Woods, R.R.; Soreq, H.; Lenz, D.E.; Cerasoli, D.M.; Mor, T.S. Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents. Proc. Natl. Acad. Sci. USA, 2010, 107(47), 20251-20256. [http://dx.doi.org/10.1073/pnas.1009021107]. [PMID: 21059932].
[42]
Iyer, R.; Iken, B. Protein engineering of representative hydrolytic enzymes for remediation of organophosphates. Biochem. Eng. J., 2015, 94, 134-144. [http://dx.doi.org/10.1016/j.bej.2014.11.010].
[43]
Worek, F.; Seeger, T.; Goldsmith, M.; Ashani, Y.; Leader, H.; Sussman, J.S.; Tawfik, D.; Thiermann, H.; Wille, T. Efficacy of the rePON1 mutant IIG1 to prevent cyclosarin toxicity in vivo and to detoxify structurally different nerve agents in vitro. Arch. Toxicol., 2014, 88(6), 1257-1266. [http://dx.doi.org/10.1007/s00204-014-1204-z]. [PMID: 24477626].
[44]
Goldsmith, M.; Aggarwal, N.; Ashani, Y.; Jubran, H.; Greisen, P.J.; Ovchinnikov, S.; Leader, H.; Baker, D.; Sussman, J.L.; Goldenzweig, A.; Fleishman, S.J.; Tawfik, D.S. Overcoming an optimization plateau in the directed evolution of highly efficient nerve agent bioscavengers. Protein Eng. Des. Sel., 2017, 30(4), 333-345. [http://dx.doi.org/10.1093/protein/gzx003]. [PMID: 28159998].
[45]
Worek, F.; Seeger, T.; Reiter, G.; Goldsmith, M.; Ashani, Y.; Leader, H.; Sussman, J.L.; Aggarwal, N.; Thiermann, H.; Tawfik, D.S. Post-exposure treatment of VX poisoned guinea pigs with the engineered phosphotriesterase mutant C23: A proof-of-concept study. Toxicol. Lett., 2014, 231(1), 45-54. [http://dx.doi.org/10.1016/j.toxlet.2014.09.003]. [PMID: 25195526].
[46]
Melzer, M.; Chen, J.C.; Heidenreich, A.; Gäb, J.; Koller, M.; Kehe, K.; Blum, M.M. Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design. J. Am. Chem. Soc., 2009, 131(47), 17226-17232. [http://dx.doi.org/10.1021/ja905444g]. [PMID: 19894712].
[47]
Daczkowski, C.M.; Pegan, S.D.; Harvey, S.P. Engineering the organophosphorus acid anhydrolase enzyme for increased catalytic efficiency and broadened stereospecificity on Russian VX. Biochemistry, 2015, 54(41), 6423-6433. [http://dx.doi.org/10.1021/acs.biochem.5b00624]. [PMID: 26418828].
[48]
Jun, D.; Musilová, L.; Link, M.; Loiodice, M.; Nachon, F.; Rochu, D.; Renault, F.; Masson, P. Preparation and characterization of methoxy polyethylene glycol-conjugated phosphotriesterase as a potential catalytic bioscavenger against organophosphate poisoning. Chem. Biol. Interact., 2010, 187(1-3), 380-383. [http://dx.doi.org/10.1016/j.cbi.2010.03.017]. [PMID: 20230809].
[49]
Bajaj, P.; Tripathy, R.K.; Aggarwal, G.; Pande, A.H. Human paraoxonase 1 as a pharmacologic agent: limitations and perspectives. ScientificWorldJournal, 2014.2014854391 [http://dx.doi.org/10.1155/2014/854391]. [PMID: 25386619].
[50]
Billecke, S.; Draganov, D.; Counsell, R.; Stetson, P.; Watson, C.; Hsu, C.; La Du, B.N. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab. Dispos., 2000, 28(11), 1335-1342. [PMID: 11038162].
[51]
Aharoni, A.; Gaidukov, L.; Yagur, S.; Toker, L.; Silman, I.; Tawfik, D.S. Directed evolution of mammalian paraoxonases PON1 and PON3 for bacterial expression and catalytic specialization. Proc. Natl. Acad. Sci. USA, 2004, 101(2), 482-487. [http://dx.doi.org/10.1073/pnas.2536901100]. [PMID: 14695884].
[52]
Harel, M.; Aharoni, A.; Gaidukov, L.; Brumshtein, B.; Khersonsky, O.; Meged, R.; Dvir, H.; Ravelli, R.B.; McCarthy, A.; Toker, L.; Silman, I.; Sussman, J.L.; Tawfik, D.S. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat. Struct. Mol. Biol., 2004, 11(5), 412-419. [http://dx.doi.org/10.1038/nsmb767]. [PMID: 15098021].
[53]
Ben-David, M.; Elias, M.; Filippi, J.J.; Duñach, E.; Silman, I.; Sussman, J.L.; Tawfik, D.S. Catalytic versatility and backups in enzyme active sites: The case of serum paraoxonase 1. J. Mol. Biol., 2012, 418(3-4), 181-196. [http://dx.doi.org/10.1016/j.jmb.2012.02.042]. [PMID: 22387469].
[54]
Ben-David, M.; Wieczorek, G.; Elias, M.; Silman, I.; Sussman, J.L.; Tawfik, D.S. Catalytic metal ion rearrangements underline promiscuity and evolvability of a metalloenzyme. J. Mol. Biol., 2013, 425(6), 1028-1038. [http://dx.doi.org/10.1016/j.jmb.2013.01.009]. [PMID: 23318950].
[55]
Costa, L.G.; Giordano, G.; Furlong, C.E. Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: The hunt goes on. Biochem. Pharmacol., 2011, 81(3), 337-344. [http://dx.doi.org/10.1016/j.bcp.2010.11.008]. [PMID: 21093416].
[56]
Gupta, R.D.; Goldsmith, M.; Ashani, Y.; Simo, Y.; Mullokandov, G.; Bar, H.; Ben-David, M.; Leader, H.; Margalit, R.; Silman, I.; Sussman, J.L.; Tawfik, D.S. Directed evolution of hydrolases for prevention of G-type nerve agent intoxication. Nat. Chem. Biol., 2011, 7(2), 120-125. [http://dx.doi.org/10.1038/nchembio.510]. [PMID: 21217689].
[57]
Goldsmith, M.; Ashani, Y.; Simo, Y.; Ben-David, M.; Leader, H.; Silman, I.; Sussman, J.L.; Tawfik, D.S. Evolved stereoselective hydrolases for broad-spectrum G-type nerve agent detoxification. Chem. Biol., 2012, 19(4), 456-466. [http://dx.doi.org/10.1016/j.chembiol.2012.01.017]. [PMID: 22520752].
[58]
Mata, D.G.; Sabnekar, P.; Watson, C.A.; Rezk, P.E.; Chilukuri, N. Assessing the stoichiometric efficacy of mammalian expressed paraoxonase-1 variant I-F11 to afford protection against G-type nerve agents. Chem. Biol. Interact, 2012, 259(Pt B), 233-241. [https://doi.org/10.1016/j.cbi.2016.04.013] [PMID: 27083144]
[59]
Timperley, C.M.; Abdollahi, M.; Al-Amri, A.S.; Baulig, A.; Benachour, D.; Borrett, V.; Cariño, F.A.; Geist, M.; Gonzalez, D.; Kane, W.; Kovarik, Z.; Martínez-Álvarez, R.; Fusaro Mourão, N.M.; Neffe, S.; Raza, S.K.; Rubaylo, V.; Suárez, A.G.; Takeuchi, K.; Tang, C.; Trifirò, F.; van Straten, F.M.; Vanninen, P.S.; Vučinić, S.; Zaitsev, V.; Zafar-Uz-Zaman, M.; Zina, M.S.; Holen, S.; Forman, J.E.; Alwan, W.S.; Suri, V. Advice on assistance and protection from the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 2. On preventing and treating health effects from acute, prolonged, and repeated nerve agent exposure, and the identification of medical countermeasures able to reduce or eliminate the longer term health effects of nerve agents. Toxicology, 2019, 413, 13-23. [http://dx.doi.org/10.1016/j.tox.2018.11.009]. [PMID: 30500381].
[60]
Flannery, B.M.; Bruun, D.A.; Rowland, D.J.; Banks, C.N.; Austin, A.T.; Kukis, D.L.; Li, Y.; Ford, B.D.; Tancredi, D.J.; Silverman, J.L.; Cherry, S.R.; Lein, P.J. Persistent neuroinflammation and cognitive impairment in a rat model of acute diisopropylfluorophosphate intoxication. J. Neuroinflammation, 2016, 13(1), 267. [http://dx.doi.org/10.1186/s12974-016-0744-y]. [PMID: 27733171].
[61]
Li, Y.; Lein, P.J.; Ford, G.D.; Liu, C.; Stovall, K.C.; White, T.E.; Bruun, D.A.; Tewolde, T.; Gates, A.S.; Distel, T.J.; Surles-Zeigler, M.C.; Ford, B.D. Neuregulin-1 inhibits neuroinflammatory responses in a rat model of organophosphate-nerve agent-induced delayed neuronal injury. J. Neuroinflammation, 2015, 12, 64. [http://dx.doi.org/10.1186/s12974-015-0283-y]. [PMID: 25880399].
[62]
Hosseini, A.; Abdollahi, M. Diabetic neuropathy and oxidative stress: Therapeutic perspectives. Oxid. Med. Cell. Longev., 2013.2013168039 [http://dx.doi.org/10.1155/2013/168039]. [PMID: 23738033].
[63]
Dhote, F.; Peinnequin, A.; Carpentier, P.; Baille, V.; Delacour, C.; Foquin, A.; Lallement, G.; Dorandeu, F. Prolonged inflammatory gene response following soman-induced seizures in mice. Toxicology, 2007, 238(2-3), 166-176. [http://dx.doi.org/10.1016/j.tox.2007.05.032]. [PMID: 17662515].
[64]
Banks, C.N.; Lein, P.J. A review of experimental evidence linking neurotoxic organophosphorus compounds and inflammation. Neurotoxicology, 2012, 33(3), 575-584. [http://dx.doi.org/10.1016/j.neuro.2012.02.002]. [PMID: 22342984].
[65]
Aharoni, S.; Aviram, M.; Fuhrman, B. Paraoxonase 1 (PON1) reduces macrophage inflammatory responses. Atherosclerosis, 2013, 228(2), 353-361. [http://dx.doi.org/10.1016/j.atherosclerosis.2013.03.005]. [PMID: 23582715].
[66]
Mahrooz, A. Pharmacological interactions of paraoxonase 1 (PON 1): A HDL-bound antiatherogenic enzyme. Curr. Clin. Pharmacol., 2016, 11(4), 259-264. [http://dx.doi.org/10.2174/1574884711666160915153433]. [PMID: 27633038].
[67]
Shunmoogam, N.; Naidoo, P.; Chilton, R. Paraoxonase (PON)-1: A brief overview on genetics, structure, polymorphisms and clinical relevance. Vasc. Health Risk Manag., 2018, 14, 137-143. [http://dx.doi.org/10.2147/VHRM.S165173]. [PMID: 29950852].
[68]
Fuhrman, B. Regulation of hepatic paraoxonase-1 expression. J. Lipids, 2012.2012684010 [http://dx.doi.org/10.1155/2012/684010]. [PMID: 22548179].
[69]
Duysen, E.G.; Bartels, C.F.; Lockridge, O. Wild-type and A328W mutant human butyrylcholinesterase tetramers expressed in Chinese hamster ovary cells have a 16-hour half-life in the circulation and protect mice from cocaine toxicity. J. Pharmacol. Exp. Ther., 2002, 302(2), 751-758. [http://dx.doi.org/10.1124/jpet.102.033746]. [PMID: 12130740].
[70]
Khersonsky, O.; Roodveldt, C.; Tawfik, D.S. Enzyme promiscuity: evolutionary and mechanistic aspects. Curr. Opin. Chem. Biol., 2006, 10(5), 498-508. [http://dx.doi.org/10.1016/j.cbpa.2006.08.011]. [PMID: 16939713].
[71]
Worek, F.; Thiermann, H.; Wille, T. Catalytic bioscavengers in nerve agent poisoning: A promising approach? Toxicol. Lett., 2016, 244, 143-148. [http://dx.doi.org/10.1016/j.toxlet.2015.07.012]. [PMID: 26200600].
[72]
Kirby, S.D.; Norris, J.R.; Richard Smith, J.; Bahnson, B.J.; Cerasoli, D.M. Human paraoxonase double mutants hydrolyze V and G class organophosphorus nerve agents. Chem. Biol. Interact., 2013, 203(1), 181-185. [http://dx.doi.org/10.1016/j.cbi.2012.10.023]. [PMID: 23159884].
[73]
Mackness, M.; Mackness, B. Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles. Gene, 2015, 567(1), 12-21. [http://dx.doi.org/10.1016/j.gene.2015.04.088]. [PMID: 25965560].
[74]
Palomares, L.A.; Estrada-Mondaca, S.; Ramírez, O.T. Production of recombinant proteins: Challenges and solutions. Methods Mol. Biol., 2004, 267, 15-52. [http://dx.doi.org/10.1385/1-59259-774-2:015]. [PMID: 15269414].
[75]
Altenbuchner, J.; Mattes, R. Escherichia coli. In: Production of recombinant proteins: Novel microbial and eukaryotic expression systems; Gellisen, G., Ed.; Wiley-VCH Verlag GmbH & Co: Weinheim, 2005; pp. 7-44.
[76]
Lilie, H.; Schwarz, E.; Rudolph, R. Advances in refolding of proteins produced in E. coli. Curr. Opin. Biotechnol., 1998, 9(5), 497-501. [http://dx.doi.org/10.1016/S0958-1669(98)80035-9]. [PMID: 9821278].
[77]
Gräslund, S.; Nordlund, P.; Weigelt, J.; Hallberg, B.M.; Bray, J.; Gileadi, O.; Knapp, S.; Oppermann, U.; Arrowsmith, C.; Hui, R.; Ming, J. dhe-Paganon, S.; Park, H.W.; Savchenko, A.; Yee, A.; Edwards, A.; Vincentelli, R.; Cambillau, C.; Kim, R.; Kim, S.H.; Rao, Z.; Shi, Y.; Terwilliger, T.C.; Kim, C.Y.; Hung, L.W.; Waldo, G.S.; Peleg, Y.; Albeck, S.; Unger, T.; Dym, O.; Prilusky, J.; Sussman, J.L.; Stevens, R.C.; Lesley, S.A.; Wilson, I.A.; Joachimiak, A.; Collart, F.; Dementieva, I.; Donnelly, M.I.; Eschenfeldt, W.H.; Kim, Y.; Stols, L.; Wu, R.; Zhou, M.; Burley, S.K.; Emtage, J.S.; Sauder, J.M.; Thompson, D.; Bain, K.; Luz, J.; Gheyi, T.; Zhang, F.; Atwell, S.; Almo, S.C.; Bonanno, J.B.; Fiser, A.; Swaminathan, S.; Studier, F.W.; Chance, M.R.; Sali, A.; Acton, T.B.; Xiao, R.; Zhao, L.; Ma, L.C.; Hunt, J.F.; Tong, L.; Cunningham, K.; Inouye, M.; Anderson, S.; Janjua, H.; Shastry, R.; Ho, C.K.; Wang, D.; Wang, H.; Jiang, M.; Montelione, G.T.; Stuart, D.I.; Owens, R.J.; Daenke, S.; Schütz, A.; Heinemann, U.; Yokoyama, S.; Büssow, K.; Gunsalus, K.C. Protein production and purification. Nat. Methods, 2008, 5(2), 135-146. [http://dx.doi.org/10.1038/nmeth.f.202]. [PMID: 18235434].
[78]
Baneyx, F. Recombinant protein expression in Escherichia coli. Curr. Opin. Biotechnol., 1999, 10(5), 411-421. [http://dx.doi.org/10.1016/S0958-1669(99)00003-8]. [PMID: 10508629].
[79]
Rosano, G.L.; Ceccarelli, E.A. Recombinant protein expression in Escherichia coli: Advances and challenges. Front. Microbiol., 2014, 5, 172. [http://dx.doi.org/10.3389/fmicb.2014.00172]. [PMID: 24860555].
[80]
Bajaj, P.; Tripathy, R.K.; Aggarwal, G.; Pande, A.H. Expression and purification of biologically active recombinant human paraoxonase 1 from inclusion bodies of Escherichia coli. Protein Expr. Purif., 2015, 115, 95-101. [http://dx.doi.org/10.1016/j.pep.2015.05.011]. [PMID: 26003526].
[81]
Stevens, R.C.; Suzuki, S.M.; Cole, T.B.; Park, S.S.; Richter, R.J.; Furlong, C.E. Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning. Proc. Natl. Acad. Sci. USA, 2008, 105(35), 12780-12784. [http://dx.doi.org/10.1073/pnas.0805865105]. [PMID: 18711144].
[82]
Tawfik, D.S.; Aharoni, A.; Gaydukov, L.; Sussman, J.L.; Silman, I. PON polypeptides, polynucleotides encoding same and compositions and methods utilizing same US Patent 7,786,071 B2., 31, 2010.
[83]
Garcıa-Fruitos, E.; Vazquez, E.; Diez-Gil, C. Bacterial inclusion bodies: Making gold from waste. Trends Biotechnol., 2012, 30, 65-70. [http://dx.doi.org/10.1016/j.tibtech.2011.09.003].
[84]
Baneyx, F.; Mujacic, M. Recombinant protein folding and misfolding in Escherichia coli. Nat. Biotechnol., 2004, 22(11), 1399-1408. [http://dx.doi.org/10.1038/nbt1029]. [PMID: 15529165].
[85]
Mayer, M.; Buchner, J. Refolding of inclusion body proteins. Methods Mol. Med., 2004, 94, 239-254. [PMID: 14959834].
[86]
Wirth, T.; Parker, N.; Ylä-Herttuala, S. History of gene therapy. Gene, 2013, 525(2), 162-169. [http://dx.doi.org/10.1016/j.gene.2013.03.137]. [PMID: 23618815].
[87]
Kontermann, R.E. Half-life extended biotherapeutics. Expert Opin. Biol. Ther., 2016, 16(7), 903-915. [http://dx.doi.org/10.1517/14712598.2016.1165661]. [PMID: 26967759].
[88]
Alconcel, S.N.S.; Baas, A.S.; Maynard, H.D. FDA-approved poly (ethylene glycol)-protein conjugate drugs. Polym. Chem., 2011, 2, 1442-1448. [http://dx.doi.org/10.1039/c1py00034a].
[89]
Strohl, W.R. Fusion proteins for half-life extension of biologics as a strategy to make biobetters. BioDrugs, 2015, 29(4), 215-239. [http://dx.doi.org/10.1007/s40259-015-0133-6]. [PMID: 26177629].
[90]
De Groot, A.S.; Scott, D.W. Immunogenicity of protein therapeutics. Trends Immunol., 2007, 28(11), 482-490. [http://dx.doi.org/10.1016/j.it.2007.07.011]. [PMID: 17964218].
[91]
Fernández, L.; Bustos, R.H.; Zapata, C.; García, J.; Jaúregui, E.; Ashraf, G.M. Immunogenicity in protein and peptide basedtherapeutics: An overview. Curr. Protein Pept. Sci., 2017, 18, 1-18.
[92]
Schellekens, H. The immunogenicity of therapeutic proteins. Discov. Med., 2010, 9(49), 560-564. [PMID: 20587346].
[93]
Bajaj, P.; Tripathy, R.K.; Aggarwal, G.; Datusalia, A.K.; Sharma, S.S.; Pande, A.H. Refolded recombinant human paraoxonase 1 variant exhibits prophylactic activity against organophosphate poisoning. Appl. Biochem. Biotechnol., 2016, 180(1), 165-176. [http://dx.doi.org/10.1007/s12010-016-2091-y]. [PMID: 27131877].
[94]
Ferrer-Miralles, N.; Domingo-Espín, J.; Corchero, J.L.; Vázquez, E.; Villaverde, A. Microbial factories for recombinant pharmaceuticals. Microb. Cell Fact., 2009, 8, 17. [http://dx.doi.org/10.1186/1475-2859-8-17]. [PMID: 19317892].
[95]
Porter, S. Human immune response to recombinant human proteins. J. Pharm. Sci., 2001, 90(1), 1-11. [http://dx.doi.org/10.1002/1520-6017(200101)90:1<1:AID-JPS1>3.0.CO;2-K]. [PMID: 11064373].
[96]
Mitragotri, S.; Burke, P.A.; Langer, R. Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies. Nat. Rev. Drug Discov., 2014, 13(9), 655-672. [http://dx.doi.org/10.1038/nrd4363]. [PMID: 25103255].
[97]
Zheng, J.C.; Lei, N.; He, Q.C.; Hu, W.; Jin, J.G.; Meng, Y.; Deng, N.H.; Meng, Y.F.; Zhang, C.J.; Shen, F.B. PEGylation is effective in reducing immunogenicity, immunotoxicity, and hepatotoxicity of α-momorcharin in vivo. Immunopharmacol. Immunotoxicol., 2012, 34(5), 866-873. [http://dx.doi.org/10.3109/08923973.2012.666979]. [PMID: 22439816].
[98]
Department of Defense, Fiscal Year (FY) 2019 Budget Estimates. Chemical and Biological Defense Program, Defense-Wide Justification Book Volume 4 of 5, Research, Development, Test & Evaluation. Defense-Wide, 2018, 1-476.
[99]
Aebersold. P. FDA Experience with medical countermeasures under the animal rule. Adv. Prev. Med., 2012, 2012, 1-11.
[100]
Pereira, E.F.; Aracava, Y.; DeTolla, L.J., Jr; Beecham, E.J.; Basinger, G.W., Jr; Wakayama, E.J.; Albuquerque, E.X. Animal models that best reproduce the clinical manifestations of human intoxication with organophosphorus compounds. J. Pharmacol. Exp. Ther., 2014, 350(2), 313-321. [http://dx.doi.org/10.1124/jpet.114.214932]. [PMID: 24907067].

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy