공업화학 (Applied Chemistry for Engineering)

  • 제35권4호
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  • Pages.284-295
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  • 2024
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  • 1225-0112(pISSN)
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  • 2288-4505(eISSN)
한국공업화학회 (The Korean Society of Industrial and Engineering Chemistry)
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신경작용제 해독 기술 동향

Trends in Antidote Technologies for Nerve Agents

  • 김성일 (화생방방재연구소) ;
  • 정진광 (육군사관학교 물리화학과) ;
  • 김동욱 (육군사관학교 물리화학과) ;
  • 황승율 (화학물질안전원 화학사고조사팀) ;
  • 조윤제 (화학물질안전원 화학사고조사팀) ;
  • 윤영욱 (화학물질안전원 화학사고조사팀) ;
  • 류태인 (화학물질안전원 화학사고조사팀) ;
  • 정근홍 (육군사관학교 물리화학과)
  • Sungyiel Kim (BRN Emergency Management Institute) ;
  • Jinkwang Jeong (Department of Physics and Chemistry, Korea Military Academy) ;
  • Dongwook Kim (Department of Physics and Chemistry, Korea Military Academy) ;
  • Seungyul Hwang (Chemical Accident Investigation Team, National Institute of Chemical Safety) ;
  • Yoonje Cho (Chemical Accident Investigation Team, National Institute of Chemical Safety) ;
  • Yeongwook Yoon (Chemical Accident Investigation Team, National Institute of Chemical Safety) ;
  • Taein Ryu (Chemical Accident Investigation Team, National Institute of Chemical Safety) ;
  • Keunhong Jeong (Department of Physics and Chemistry, Korea Military Academy)
  • 투고 : 2024.07.09
  • 심사 : 2024.07.18
  • 발행 : 2024.08.10
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초록

화학작용제는 독성 매커니즘에 따라 신경작용제, 질식작용제, 혈액작용제, 수포작용제 등으로 분류한다. 이 중 신경작용제는 채내에서 신경전달물질을 분해하는 AChE와 결합하여 자율신경계를 교란하여 독성 증상을 나타낸다. 심한 경우 사망에 이르게 하는 치명적인 화학작용제이다. 따라서, 인체 내 침투 후에는 신속하게 해독하는 것이 중요하다. 해독을 위해 사용되는 해독제는 화학 의약품으로 전처치제, 후처치제, 항경련제, 바이오스캐빈저 등이 사용되고 있다. 본 리뷰에서는 신경작용제 해독제의 용도, 형태, 구성성분 및 해독원리와 바이오스캐빈저의 연관성을 다루게 될 것이다.

Chemical agents are classified according to their mechanism of toxicity into categories such as nerve agents, choking agents, blood agents, blister agents, etc. Among them, nerve agents cause toxic symptoms by binding with acetylcholinesterase (AChE) in the body, which breaks down neurotransmitters, thus disrupting the autonomic nervous system. In severe cases, this can lead to death, making it a critical chemical agent. Therefore, once it has penetrated into the human body, it is important to detoxify it swiftly. Antidotes used for detoxification include chemical medicines such as pretreatment agents, post-treatment agents, anticonvulsants, and bioscavengers. This review will address the uses, forms, components, and principles of detoxification of nerve agent antidotes and the association with bioscavengers.

키워드

과제정보

해당연구는 화학물질안전원의 연구지원에 의하여 수행되었으며, 이에 감사드립니다.

참고문헌

  1. S. D. Lee, I. W. Yang, W. Y. Jung, Y. S. Kye, S. I. Kim, and D. W. Kim, Detoxification and treatment of chemicla agents, Military Chemical, 1st ed., 419-423, Bongmyang, Seoul, Korea (2002).
  2. S. D. Lee, I. W. Yang, W. Y. Jung, Y. S. Kye, S. I. Kim, and D. W. Kim, Neural transmission, Military Chemical, 1st ed., 405-408, Bongmyang, Seoul, Korea (2002).
  3. I. B. Wilson and B. Ginsburg, A powerful reactivator of alkylphosphate-inhibited acetylcholinesterase, Biochim. Biophys. Acta, 18, 168-170 (1955).
  4. M. A. Dunn and F. R. Sidell, Progress in medical defence against nerve agents, JAMA, 262, 649-652 (1989).
  5. C. Luo, A. Saxena, M. Smith, G. Garcia, Z. Radic, P. Taylor, and B. P. Doctor, Phosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium, Biochemistry, 38, 9937-9947 (1999).
  6. B. A. Golomb, Acetylcholinesterase inhibitors and Gulf War illnesses, Proc. Natl. Acad. Sci. U.S.A., 105, 4295-4300 (2008).
  7. F. R. Sidell and J. Borak, Chemical warfare agents: II. Nerve agents, Ann. Emerg. Med., 21, 865-871 (1992).
  8. Atromat - Atropine automatic injector (Shalon Chemical Industries Ltd), https://www.shalon.co.il/html5/ProLookup.taf?_ID=40603&did=22079&G=14541&SM=14768 (2024.7.25.).
  9. Fact sheet for healthcare providers: EUA of atropine auto-injector (Rafa Laboratories Ltd.), https://www.fda.gov/media/104559/ (2022. 9.30.).
  10. K. W. Lee, S. Y. An, and B. G. Hur, A case study on the FDA approval of medical treatments against nerve agent poisoning, J. KIMS Technol., 19, 119-126 (2016).
  11. P. Eyer, M. Eddleston, H. Thiermann, F. Worek, and N. A. Buckley, Are we using the right dose? A tale of mole and gram, Br. J. Clin. Pharmacol., 66, 451-452 (2016).
  12. H. Thiermann, L. Szinicz, F. Eyer, F. Worek, P. Eyer, N. Felgenhauer, and T. Zilker, Modern strategies in therapy of organophosphate poisoning, Toxicol. Lett., 107, 233-239 (1999).
  13. E. Nepovimova and K. Kuca, Chemical warfare agent NOVICHOK: Mini-review of available data, Food Chem. Toxicol., 121, 343-350 (2018).
  14. M. Eddleston, N. A.Buckley, P. Eyer, and A. H. Dawson, Management of acute organophosphorus pesticide poisoning, Lancet, 371, 597-607 (2008).
  15. K. Sakurada, K. Matsubara, K. Shimizu, H. Shiono, Y. Seto, K. Tsuge, M. Yoshino, I. Sakai, H. Mukoyama, and T. Takatori, Pralidoxime iodide(2-PAM) penetrates across the blood-brain barrier, Neurochem. Res., 28, 1401-1407 (2003).
  16. M. Jokanovic, M. P. Stojiljkovic, B. Kovac, and D. Ristic, Pyridinium oximes in the treatment of poisoning with organophosphorus compounds, In: R. C. Gupta (ed.). Handbook of Toxicology of Chemical Warfare Agents, 3rd ed., 1145-1159, Academic Press, Cambridge, Massachusetts, USA, (2020).
  17. F. Worek, M. Backer, H. Thiermann, L. Szinicz, U. Mast, R. Klimmek, and P. Eyer, Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning, Hum. Exp. Toxicol., 16, 466-472 (1997).
  18. P. Eyer, The role of oximes in the management of organophosphorus pesticide poisoning, Toxicol. Review, 22, 165-190 (2003).
  19. J. G. Clement, HI-6: Reactivation of central and peripheral acetylcholinesterase following inhibition by soman, sarin and tabun in vivo in the rat, Biochem. Pharmacol., 31, 1283-1287 (1982).
  20. M. C. Santos, F. D. Botelho, A. S.Goncalves, D. A. S.Kitagawa, C. V. N. Borges, T. Carvalho-Silva, L. B. Bernardo, C. N. Ferreira, R. B. Rodrigues, D. C. F. Neto, E. Nepovimova, K. Kuca, S. R. LaPlante, A. L. S. Lima, T. C. C. Franca, and S. F. A. Cavalcante., Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series?, Arch. Toxicol., 96, 2559-2572 (2022).
  21. Protection materiel, Samyangchemcal Co. Ltd., https://samyangchem.com/product_02/ (2024.7.25.).
  22. Multiservice Tactics, Techniques, and Procedures for Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries, Federation of American Scientists, https://irp.fas.org/doddir/army/fm4-02-285.pdf (2024.7.25.).
  23. ATNAA Prescribing Information, Drugs.com, https://www.drugs.com/pro/atnaa.html (2024.7.25.).
  24. J. Doyle, "Local plant suspends production of nerve gas antidote", STL Today, 2013.11.3.
  25. J. Swaine, The government spent tens of millions on a treatment for chemical weapons exposure. The company that makes it won't say whether it works., The Washington Post, 2020.8.18.
  26. M. J. A. Joosena, S. D. Klaassena, E. Verheija, T. van Groningena, A. S. Cornelissena, M. H. Skiadopoulosb, L. Cochraneb, and J. D. Shearer, Efficacy of atropine sulfate/obidoxime chloride co-formulation against sarin exposure in guinea pigs, Chem. Biol. Interact., 296, 34-429 (2018).
  27. J. Kentrop, V. Savranskyc, S. D. Klaassena, T. van Groningena, S. B. Alex, S. Cornelissena, L. Cochranec, J. B. Marloes, and J. A. Joosena, Pharmacokinetics and efficacy of atropine sulfate & obidoxime chloride co-formulation against VX in a guinea pig model, Regul. Toxicol. Pharmacol., 119, 104823. (2021).
  28. R. Silbergleit, D. Lowenstein, V. Durkalski, and R. Conwit, RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): A double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia, 52, 45-47 (2011).
  29. F. Detrick, FDA approves new drug application for the DoD's advanced anticonvulsant system program, JPEO-CBRND News, https://www.jpeocbrnd.osd.mil/Media/News/Article/3137708/, 2022.8.24.
  30. T. Myhrer and P. Aas, Pretreatment and prophylaxis against nerve agent poisoning: Are undesirable behavioral side effects unavoidable?, Neurosci. Biobehav. Rev., 71, 657-670 (2016).
  31. P. Masson, M. T. Froment, C. F. Bartels, and O. Lockridge, Importance of aspartate-70 in organophosphate inhibition, oxime re-activation and aging of human butyrylcholinesterase, Biochem. J., 325, 53-61 (1997).
  32. S. V. Lushchekina, L. M. Schopfer, B. L. Grigorenko, A. V. Nemukhin, S. D. Varfolomeev, O. Lockridge, and P. Masson, Optimization of cholinesterase-based catalytic bioscavengers against organophosphorus agents, Front. Pharmacol., 9, 211 (2018).
  33. B. P. Doctor and A. Saxena, Bioscavengers for the protection of humans against organophosphate toxicity, Chem. Biol. Interact., 157-158, 167-171. (2005).
  34. H. Mumford, C. J. Docx, M. E. Price, A. C. Green, J. E. H. Tattersall, and S. J. Armstrong, Human plasma-derived BuChE as a stoichiometric bioscavenger for treatment of nerve agent poisoning, Chem. Biol. Interact., 203, 160-166 (2013).
  35. F. Worek, H. Thiermann, and T. Wille, Catalytic bioscavengers in nerve agent poisoning: a promising approach?, Toxicol. Lett., 244, 143-148 (2016).
  36. O. Lockridge, Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses, Pharmacol. Therapeut., 148, 34-46 (2015).
  37. Y. Ashani and S. Pistinner, Estimation of the upper limit of human butyrylcholinesterase dose required for protection against organophosphates toxicity: A mathematically based toxicokinetic model, Toxicol. Sci., 77, 358-367 (2004).
  38. J. M. Corbin, B. I. Hashimoto, K. Karuppanan, Z. R. Kyser, L. Wu, B. A. Roberts, A. R. Noe, R. L. Rodriguez, K. A. McDonald, and S. Nandi, Semicontinuous bioreactor production of recombinant butyrylcholinesterase in transgenic rice cell suspension cultures, Front. Plant Sci., 7, 41 (2016).
  39. J. Descotes and A. Gouraud, Clinical immunotoxicity of therapeutic proteins, Expert Opin. Drug Metab. Toxicol., 4, 1537-1549 (2008).
  40. R. Sharma, B. Gupta, N. Singh, J. R. Acharya, K. Musilek, K. Kuca, K. K. Ghosh, Development and structural modifications of cholinesterase reactivators against chemical warfare agents in last decade: A review, Mini-Rev. Med. Chem., 15, 58-72 (2015).
  41. P. Masson and S. V. Lushchekina, Emergence of catalytic bioscavengers against organophosphorus agents, Chem. Biol. Interact., 259, 319-326 (2016).
  42. Y. Ashani, H. Leader, N. Aggarwal, I. Silman, F. Worek, J. L. Sussman, and M. Goldsmith, In vitro evaluation of the catalytic activity of paraoxonases and phosphotriesterases predicts the enzyme circulatory levels required for in vivo protection against organophosphate intoxications, Chem. Biol. Interact., 259, 252-256 (2016)
  43. G. A. Alles and R. C. Hawes, Cholinesterases in the blood of man, J. Biol. Chem., 133, 375-39 (1940).
  44. C. A. Broomfield, D. M. Maxwell, R. P. Solana, C. A. Castro, A. V. Finger, and D. E. Lenz, Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates, J. Pharmacol. Exp. Ther., 259, 633-638 (1991).
  45. V. Murthy, Y. Gao, L. Geng, N. K. LeBrasseur, T. A. White, R. J. Parks, and S. Brimijoin, Physiologic and metabolic safety of butyrylcholinesterase gene therapy in mice, Vaccine, 32, 4155-4162 (2014).
  46. Y. Nicolet, O. Lockridge, P. Masson, J. C. Fontecilla-Camps, and F. Nachon, Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products, J. Biol. Chem., 278, 41141-41147 (2003).
  47. X. Brazzolotto, A. Igert, V. Guillon, G. Santoni, and F. Nachon, Bacterial expression of human butyrylcholinesterase as a tool for nerve agent bioscavengers development, Molecules, 22, 1828 (2017).
  48. B. P. Doctor, A. Saxena, W. Sun, C. Luo, P. Tipparaju, I. Koplovitz, D. E. Lenz, and M. C. Ross, Large-scale production of human serum butyrylcholinesterase as a bioscavenger, US Patent 7754461 B2 (2010).
  49. P. Li, S. Y. Moon, M. A. Guelta, L. Lin, D. A. Gomez-Gualdro, R. Q. Snurr, S. P. Harvey, J. T. Hupp, and O. K. Farha, Nanosizing a metal-organic framework enzyme carrier for accelerating nerve agent hydrolysis, ACS Nano, 10, 9174-9182 (2016).
  50. Civil Action No. 1:19-cv-02092-RDB Document 27, August 26, United States District Court for the District of Maryland (2019).
  51. Civil Action No. 19-cv-02092-LKG Document 154, April 5, In the United States District Court for the District of Maryland (2022).
  52. W. N. Aldridge, Serum esterases I. Two types of esterase (A and B) hydrolysing p-nitrophenyl acetate, propionate and butyrate, and a method for their determination, Biochem. J., 53, 110-117 (1953).
  53. J. Estevez and E. Vilanova, Model equations for the kinetics of covalent irreversible enzyme inhibition and spontaneous reactivation: Esterases and organophosphorus compounds, Crit. Rev. Toxicol., 39, 427-448 (2009).
  54. M. Katalinic, N. M. Hrvat, K. Baumann, S. M. Pipercic, S. Makaric, S. Tomic, O. Jovic, T. Hrenar, A. Milicevic, D. Jelic, S. Zunec, I. Primozic, and Z. Kovarik, A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase-based nerve agent bioscavengers, Toxicol. Appl. Pharmacol., 310, 195-204 (2016).
  55. N. M. Hrvat, S. Zunec, P. Taylor, Z. Radic, and Z. Kovarik, HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants, Chem. Biol. Interact., 259, 148-153 (2016).
  56. A. Shafferman, A. Ordentlich, D. Barak, D. Stein, N. Ariel, and B. Velan, Aging of phosphylated human acetylcholinesterase: Catalytic processes mediated by aromatic and polar residues of the active centre, Biochem. J., 318, 833-840 (1996).
  57. Z. Kovarik, N. Macek Hrvat, M. Katalinic, R. K. Sit, A. Paradyse, S. Zunec, K. Musilek, V. V. Fokin, P. Taylor, and Z. Radic, Catalytic soman scavenging by the Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes, Chem. Res. Toxicol., 28, 1036-1044 (2015).
  58. F. Worek, N. Aurbek, T. Wille, P. Eyer, and H. Thiermann, Kinetic prerequisites of oximes as effective reactivators of organophosphate-inhibited acetylcholinesterase: A theoretical approach, J. Enzyme Inhib. Med. Chem., 26, 303-30 (2011).
  59. F. Worek, G. Reiter, P. Eyer, and L. Szinicz, Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates, Arch. Toxicol., 76, 523-529 (2002).
  60. M. Goldsmith and Y. Ashani, Catalytic bioscavengers as countermeasures against organophosphate nerve agents, Chem. Biol. Interact., 292, 50-64 (2018).
  61. P. Masson, F. Nachon, C. A. Broomfield, D. E. Lenz, L. Verdier, L. M.Schopfer, and O. Lockridge, A collaborative endeavor to design cholinesterase-based catalytic scavengers against toxic organophosphorus esters, Chem. Biol. Interact., 175, 273-280 (2008).
  62. Y. Ashani, H. Leader, N. Aggarwal, I. Silman, F. Worek, J. L. Sussman, and M. Goldsmith, In vitro evaluation of the catalytic activity of paraoxonases and phosphotriesterases predicts the enzyme circulatory levels required for in vivo protection against organophosphate intoxications, Chem. Biol. Interact., 259, 252-256 (2016)
  63. M. Goldsmith, S. Eckstein, Y. Ashani, P. Jr. Greisen, H. Leader, J. L. Sussman, N. Aggarwal, S. Ovchinnikov, D. S. Tawfik, D. Baker, H. Thiermann, and F. Worek, Catalytic efficiencies of directly evolved phosphotriesterase variants with structurally different organophosphorus compounds in vitro, Arch. Toxicol., 90, 2711-2724 (2016).
  64. T. Wille, K. Neumaier, M. Koller, C. Ehinger, N. Aggarwal, Y. Ashani, M. Goldsmith, J. L. Sussman, D. S. Tawfik, H. Thiermann, and F. Worek, Single treatment of VX poisoned guinea pigs with the phosphotriesterase mutant C23AL: Intraosseous versus intravenous injection, Toxicol. Lett., 258, 198-206 (2016).
  65. M. Goldsmith, N. Aggarwal, Y. Ashani, H. Jubran, P. Jr. Greisen, S. Ovchinnikov, H. Leader, D. Baker, J. L. Sussman, A. Goldenzweig, S. J. Fleishman, and D. S. Tawfik, Overcoming an optimization plateau in the directed evolution of highly efficient nerve agent bioscavengers, Protein. Eng. Des. Sel., 30, 333-345 (2017).
  66. A. N. Bigley, M. F. Mabanglo, S. P. Harvey, and F. M. Raushel, Variants of phosphotriesterase for the enhanced detoxification of the chemical warfare agent VR, Biochemistry, 54, 5502-5512 (2015).
  67. D. I. Draganov, J. F. Teiber, A. Speelman, Y. Osawa, R. Sunahara, and B. N. La Du, Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities, J. Lipid Res., 46, 1239-1247 (2005).
  68. D. A. Chistiakov, A. A. Melnichenko, A. N. Orekhov, and Y. V. Bobryshev, Paraoxonase and atherosclerosis-related cardiovascular diseases, Biochimie, 132, 19-27 (2017).
  69. L. G. Costa, G. Giordano, T. B. Cole, J. Marsillach, and C. E. Furlong, Paraoxonase 1 (PON1) as a genetic determinant of susceptibility to organophosphate toxicity, Toxicology, 307, 115-122 (2013).
  70. M. Valiyaveettil, Y. Alamneh, P. Rezk, M. W. Perkins, A. M. Sciuto, B. P. Doctor, and M. P. Nambiar, Recombinant paraoxonase 1 protects against sarin and soman toxicity following microinstillation inhalation exposure in Guinea pigs, Toxicol. Lett., 202, 203-208 (2011).
  71. R. D. Gupta, M. Goldsmith, Y. Ashani, Y. Simo, G. Mullokandov, H. Bar, M. BenDavid, H. Leader, R. Margalit, I. Silman, J. L. Sussman, and D. S. Tawfik, Directed evolution of hydrolases for prevention of G-type nerve agent intoxication, Nat. Chem. Biol., 7, 120-125 (2011).
  72. F. Worek, T. Seeger, M. Goldsmith, Y. Ashani, H. Leader, J. S. Sussman, D. Tawfik, H. Thiermann, and T. Wille, Efficacy of the rePON1 mutant IIG1 to prevent cyclosarin toxicity in vivo and to detoxify structurally different nerve agents in vitro, Arch. Toxicol., 88, 1257-1266 (2014).
  73. D. G. Mata, P. Sabnekar, C. A. Watson, P. E. Rezk, and N. Chilukuri, Assessing the stoichiometric efficacy of mammalian expressed paraoxonase-1 variant I-F11 to afford protection against G-type nerve agents, Chem. Biol. Interact., 259, 233-241 (2016).
  74. C. M. Serdar, D. T. Gibson, D. M. Munnecke, and J. H. Lancaster, Plasmid involvement in parathion hydrolysis by Pseudomonas diminuta, Appl. Environ. Microbiol., 44, 246-249 (1982).
  75. L. Afriat-Jurnou, C. J. Jackson, and D. S. Tawfik, Reconstructing a missing link in the evolution of a recently diverged phosphotriesterase by active-site loop remodeling, Biochemistry, 51, 6047-6055 (2012).
  76. D. P. Dumas, H. D. Durst, W. G. Landis, F. M. Raushel, and J. R. Wild, Inactivation of organophosphorus nerve agents by the phosphotriesterase from Pseudomonas diminuta, Arch. Biochem. Biophys., 277, 155-159 (1990).
  77. J. E. Kolakowski, J. J. DeFrank, S. P. Harvey, L. L. Szafraniec, W. T. Beaudry, K. H. Lai, and J. R. Wild, Enzymatic hydrolysis of the chemical warfare agent VX and its neurotoxic analogues by organophosphorus hydrolase, Biocatal. Biotransformation, 15, 297-312 (1997).
  78. V. K. Rastogi, J. J. DeFrank, T. C. Cheng, and J. R. Wild, Enzymatic hydrolysis of RussianVX by organophosphorus hydrolase, Biochem. Biophys. Res. Commun., 241, 294-296 (1997).
  79. F. Worek, T. Seeger, G. Reiter, M. Goldsmith, Y. Ashani, H. Leader, J. L. Sussman, N. Aggarwal, H. Thiermann, and D. S. Tawfik, Post-exposure treatment of VX poisoned Guinea pigs with the engineered phosphotriesterase mutant C23: A proof-of-concept study, Toxicol. Lett., 231, 45-54 (2014).
  80. T. Wille, K. Neumaier, M. Koller, C. Ehinger, N. Aggarwal, Y. Ashani, M. Goldsmith, J. L. Sussman, D. S. Tawfik, H. Thiermann, and F. Worek, Single treatment of VX poisoned Guinea pigs with the phosphotriesterase mutant C23AL: Intraosseous versus intravenous injection, Toxicol. Lett., 258, 198-206 (2016).
  81. F. C. Hoskin, Diisopropylphosphorofluoridate and Tabun: enzymatic hydrolysis and nerve function, Science, 172, 1243-1245 (1971).
  82. J. Gab, M. Melzer, K. Kehe, A. Richardt, and M. M. Blum, Quantification of hydrolysis of toxic organophosphates and organophosphonates by diisopropyl fluorophosphatase from Loligo vulgaris by in situ Fourier transform infrared spectroscopy, Anal. Biochem., 385, 187-193 (2009).
  83. M. Melzer, J. C. Chen, A. Heidenreich, J. Gab, M. Koller, K. Kehe, and M. M. Blum, Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design, J. Am. Chem. Soc., 131, 17226-17232 (2009).
  84. M. Melzer, A. Heidenreich, F. Dorandeu, J. Gab, K. Kehe, H. Thiermann, T. Letzel, and M. M. Blum, In vitro and in vivo efficacy of PEGylated diisopropyl fluorophosphatase(DFPase), Drug Test. Anal., 4, 262-270 (2012).
  85. J. J. DeFrank and T. C. Cheng, Purification and properties of an organophosphorus acid anhydrase from a halophilic bacterial isolate, J. Bacteriol., 173, 1938-1943 (1991).
  86. N. K. Vyas, A. Nickitenko, V. K. Rastogi, S. S. Shah, and F. A. Quiocho, Structural insights into the dual activities of the nerve agent degrading organophosphate anhydrolase/prolidase, Biochemistry, 49, 547-559 (2010).
  87. M. Matula, T. Kucera, O. Soukup, and J. Pejchal, Enzymatic degradation of organophosphorus pesticides and nerve agents by EC: 3.1.8.2, Catalysts, 10, 1365 (2020).
  88. C. M. Daczkowski, S. D. Pegan, and S. P. Harvey, Engineering the organophosphorus acid anhydrolase enzyme for increased catalytic efficiency and broadened stereospecificity on Russian VX, Biochemistry, 54, 6423-6433 (2015).
  89. S. Y. Bae, J. M. Myslinski, L. R. McMahon, J. J. Height, A. N. Bigley, F. M. Raushel, and S. P. Harvey, An OPAA enzyme mutant with increased catalytic efficiency on the nerve agents sarin, soman, and GP, Enzyme Microb. Technol., 112, 65-71 (2018).
  90. P. Wilk, M. Uehlein, J. Kalms, H. Dobbek, U. Mueller, and M. S. Weiss, Substrate specificity and reaction mechanism of human prolidase, FEBS J., 284, 2870-2885 (2017).
  91. M. Costante, L. Biggemann, Y. Alamneh, I. Soojhawon, R. Short, S. Nigam, G. Garcia, B. P. Doctor, M. Valiyaveettil, and M. P. Nambiar, Hydrolysis potential of recombinant human skin and kidney prolidase against diisopropylfluorophosphate and sarin by in vitro analysis, Toxicol. In Vitro, 26, 182-188 (2012).
  92. P. E. Rezk, P. Zdenka, P. Sabnekar, T. Kajih, D. G. Mata, C. Wrobel, D. M. Cerasoli, and N. Chilukuri, An in vitro and in vivo evaluation of the efficacy of recombinant human liver prolidase as a catalytic bioscavenger of chemical warfare nerve agents, Drug Chem. Toxicol., 38, 37-43 (2015).
  93. V. Aleti, G. B. Reddy, K. Parikh, P. Arun, and N. Chilukuri, Persistent and high-level expression of human liver prolidase in vivo in mice using adenovirus, Chem. Biol. Interact., 203, 191-195 (2013).
  94. J. C. DeMar, E. D. Clarkson, R. H. Ratcliffe, A. J. Campbell, S. G. Thangavelu, C. A. Herdman, and R. K. Gordon, Pro-2-PAM therapy for central and peripheral cholinesterases, Chem. Biol. Interact., 187, 191-198 (2010).
  95. R. Golime, M. Palit, J. Acharya, and D. K. Dubey, Neuroprotective effects of galantamine on nerve agent-induced neuroglial and biochemical changes, Neurotox. Res., 33, 738-748 (2018).
  96. E. A. Alexandrova, Y. Aracava, E. F. Pereira, and E. X. Albuquerque, Pretreatment of guinea pigs with galantamine prevents immediate and delayed effects of soman on inhibitory synaptic transmission in the hippocampus, J. Pharmacol. Exp. Ther., 334, 1051-1058 (2010).
  97. L. R. Hamilton, S. C. Schachter, and T. M. Myers, Time course, behavioral safety, and protective efficacy of centrally active reversible acetylcholinesterase inhibitors in cynomolgus macaques, Neurochem. Res., 42, 1962-1971 (2017).
  98. Y. J. Rosenberg, L. Mao, X. Jiang, J. Lees, L. Zhang, Z. Radic, and P. Taylor, Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor, Chem. Biol. Interact., 274, 50-57 (2017).
  99. B. J. Bennion, M. A. Malfatti, N. A. Be, H. A. Enright, S. Hok, C. L. Cadieux, T. S. Carpenter, V. Lao, E. A. Kuhn, M. W. McNerney, F. C. Lightstone, T. H. Nguyen, and C. A. Valdez, Development of a CNS-permeable reactivator for nerve agent exposure: An iterative, multi-disciplinary approach, Sci. Rep., 11, 15567 (2021).
  100. A. Ozgur, and Y. Tutar, Therapeutic proteins: A to Z, Protein Peptide Lett., 20, 1365-1372 (2013).
  101. K. Rehman, M. S. Hamid Akash, B. Akhtar, M. Tariq, A. Mahmood, and M. Ibrahim, Delivery of therapeutic proteins: Challenges and strategies, Curr. Drug Targets, 17, 1172-1188 (2016).
  102. C. J. Roberts, Therapeutic protein aggregation: Mechanisms, design, and control, Trends Biotechnol., 32, 372-380 (2014).
  103. A. S. Rosenberg, A. R. Pariser, B. Diamond, L. Yao, L. A. Turka, E. Lacana, and P. S. Kishnani, A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins, Clin. Immunol., 165, 55-59 (2016).
  104. H. A. Lagasse, A. Lagasse, V. L. Simhadri, N. H. Katagiri, W. Jankowski, Z. E. Sauna, and C. Kimchi-Sarfaty, Recent advances in (therapeutic protein) drug development, F1000Res., 6, 113 (2017).
  105. J. K. Dozier, and M. D. Distefano, Site-specific PEGylation of therapeutic proteins, Int. J. Mol. Sci., 16, 25831-25864 (2015).
  106. M. C. Ross, C. A. Broomfield, D. M. Cerasoli, B. P. Doctor, D. E. Lenz, D. M. Maxwell, and A. Saxena, Nerve agent bioscavenger: Development of a new approach to protect against organophosphorus exposure, In: M. K. Lenhart and S. D. Tuorinsky (eds.). Medical Aspects of Chemical Warfare, 243-259, The Office of the Surgeon General at TMM Publications, Washington, DC, USA (2008).