In vivo administration of BL-3050: Highly stable engineered PON1-HDL complexes

BMC Clinical Pharmacology

Volumn 9, Issue , 2009, Pages

  Gaidukov, Leonid ^a   Bar, Dganit ^b   Yacobson, Shiri ^a   Naftali, Esmira ^b   Kaufman, Olga ^b   Tabakman, Rinat ^b   Tawfik, Dan S ^a   Levy Nissenbaum, Etgar ^b  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b BioLine Innovations Jerusalem   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ARYLDIALKYLPHOSPHATASE 1; ATROPINE DERIVATIVE; BL 3050; CHLORPYRIFOS; PRALIDOXIME; RECOMBINANT ARYLDIALKYLPHOSPHATASE 1; RECOMBINANT ENZYME; UNCLASSIFIED DRUG; 1-PALMITOYL-2-OLEOYLPHOSPHATIDYLCHOLINE; 2 OLEOYL 1 PALMITOYLPHOSPHATIDYLCHOLINE; ARYLDIALKYLPHOSPHATASE; DRUG DERIVATIVE; GLUTATHIONE; HIGH DENSITY LIPOPROTEIN; O,O DIETHYL O 3,5,6 TRICHLORO 2 PYRIDYL PHOSPHATE; O,O-DIETHYL O-3,5,6-TRICHLORO-2-PYRIDYL PHOSPHATE; ORGANOPHOSPHATE; PHOSPHATIDYLCHOLINE; PON1 PROTEIN, HUMAN; RECOMBINANT PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG STABILITY; FEASIBILITY STUDY; FEMALE; IMMUNE RESPONSE; IN VIVO STUDY; INTOXICATION; MALE; MOUSE; NONHUMAN; OXIDATION; PROTEIN ENGINEERING; PROTEIN STRUCTURE; SINGLE DRUG DOSE; TISSUE DISTRIBUTION; TOXICITY TESTING; ANIMAL; C57BL MOUSE; CHEMISTRY; COMPARATIVE STUDY; DISEASE MODEL; DRUG ANTAGONISM; DRUG EFFECT; ENZYME STABILITY; GENETICS; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; METHODOLOGY; PHYSIOLOGY;

ANIMALS; ARYLDIALKYLPHOSPHATASE; CHLORPYRIFOS; DISEASE MODELS, ANIMAL; ENZYME STABILITY; FEMALE; GLUTATHIONE; HUMANS; INJECTIONS, INTRAVENOUS; LIPOPROTEINS, HDL; MALE; MICE; MICE, INBRED C57BL; PHOSPHATIDYLCHOLINES; PHOSPHORIC ACID ESTERS; PROTEIN ENGINEERING; RECOMBINANT PROTEINS;

EID: 71549126201     PISSN: None     EISSN: 14726904     Source Type: Journal    
DOI: 10.1186/1472-6904-9-18     Document Type: Article

References (64)

1. Khersonsky O, Tawfik DS. Structure-Reactivity Studies of Serum Paraoxonase PON1 Suggest that Its Native Activity Is Lactonase. Biochemistry 2005, 44(16):6371-6382. 10.1021/bi047440d, 15835926.
2. Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res 2005, 46(6):1239-1247. 10.1194/jlr.M400511-JLR200, 15772423.
3. Camps J, Marsillach J, Joven J. The paraoxonases: role in human diseases and methodological difficulties in measurement. Critical reviews in clinical laboratory sciences 2009, 46(2):83-106. 10.1080/10408360802610878, 19255916.
4. Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN. Human serum Paraoxonase/Arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids: apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol 1999, 19(9):2214-2225.
5. Deakin S, Leviev I, Gomaraschi M, Calabresi L, Franceschini G, James RW. Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 2002, 277(6):4301-4308. 10.1074/jbc.M107440200, 11726658.
6. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 1995, 96(6):2882-2891. 10.1172/JCI118359, 185999, 8675659.
7. Ng CJ, Shih DM, Hama SY, Villa N, Navab M, Reddy ST. The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 2005, 38(2):153-163. 10.1016/j.freeradbiomed.2004.09.035, 15607899.
8. Rosenblat M, Vaya J, Shih D, Aviram M. Paraoxonase 1 (PON1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine. Atherosclerosis 2005, 179(1):69-77. 10.1016/j.atherosclerosis.2004.10.028, 15721011.
9. Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998, 394(6690):284-287. 10.1038/28406, 9685159.
10. Bhattacharyya T, Nicholls SJ, Topol EJ, Zhang R, Yang X, Schmitt D, Fu X, Shao M, Brennan DM, Ellis SG. Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. Jama 2008, 299(11):1265-1276. 10.1001/jama.299.11.1265, 18349088.
11. Mackness M, Durrington P, Mackness B. Paraoxonase 1 activity, concentration and genotype in cardiovascular disease. Curr Opin Lipidol 2004, 15(4):399-404. 10.1097/01.mol.0000137227.54278.29, 15243212.
12. Davies HG, Richter RJ, Keifer M, Broomfield CA, Sowalla J, Furlong CE. The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat Genet 1996, 14(3):334-336. 10.1038/ng1196-334, 8896566.
13. Amitai G, Gaidukov L, Adani R, Yishay S, Yacov G, Kushnir M, Teitlboim S, Lindenbaum M, Bel P, Khersonsky O. Enhanced stereoselective hydrolysis of toxic organophosphates by directly evolved variants of mammalian serum paraoxonase. Febs J 2006, 273(9):1906-1919. 10.1111/j.1742-4658.2006.05198.x, 16640555.
14. Li WF, Costa LG, Richter RJ, Hagen T, Shih DM, Tward A, Lusis AJ, Furlong CE. Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds. Pharmacogenetics 2000, 10(9):767-779. 10.1097/00008571-200012000-00002, 11191881.
15. Li WF, Furlong CE, Costa LG. Paraoxonase protects against chlorpyrifos toxicity in mice. Toxicol Lett 1995, 76(3):219-226. 10.1016/0378-4274(95)80006-Y, 7539166.
16. Ferretti G, Bacchetti T, Marchionni C, Caldarelli L, Curatola G. Effect of glycation of high density lipoproteins on their physicochemical properties and on paraoxonase activity. Acta Diabetol 2001, 38(4):163-169. 10.1007/s592-001-8074-z, 11855794.
17. Jaouad L, Milochevitch C, Khalil A. PON1 paraoxonase activity is reduced during HDL oxidation and is an indicator of HDL antioxidant capacity. Free Radic Res 2003, 37(1):77-83. 10.1080/1071576021000036614, 12653220.
18. Rozenberg O, Aviram M. S-Glutathionylation regulates HDL-associated paraoxonase 1 (PON1) activity. Biochem Biophys Res Commun 2006, 351(2):492-498. 10.1016/j.bbrc.2006.10.059, 17070779.
19. Hedrick CC, Thorpe SR, Fu MX, Harper CM, Yoo J, Kim SM, Wong H, Peters AL. Glycation impairs high-density lipoprotein function. Diabetologia 2000, 43(3):312-320. 10.1007/s001250050049, 10768092.
20. Moren X, Deakin S, Liu ML, Taskinen MR, James RW. HDL subfraction distribution of paraoxonase-1 and its relevance to enzyme activity and resistance to oxidative stress. J Lipid Res 2008, 49(6):1246-1253. 10.1194/jlr.M700439-JLR200, 18314464.
21. Rosenblat M, Gaidukov L, Khersonsky O, Vaya J, Oren R, Tawfik DS, Aviram M. The catalytic histidine dyad of high density lipoprotein-associated serum paraoxonase-1 (PON1) is essential for PON1-mediated inhibition of low density lipoprotein oxidation and stimulation of macrophage cholesterol efflux. J Biol Chem 2006, 281(11):7657-7665. 10.1074/jbc.M512595200, 16407304.
22. Rosenblat M, Karry R, Aviram M. Paraoxonase 1 (PON1) is a more potent antioxidant and stimulant of macrophage cholesterol efflux, when present in HDL than in lipoprotein-deficient serum: relevance to diabetes. Atherosclerosis 2006, 187(1):74-81. 10.1016/j.atherosclerosis.2005.08.026, 16229851.
23. Kontush A, Chapman MJ. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 2006, 58(3):342-374. 10.1124/pr.58.3.1, 16968945.
24. Navab M, Hama-Levy S, Van Lenten BJ, Fonarow GC, Cardinez CJ, Castellani LW, Brennan ML, Lusis AJ, Fogelman AM, La Du BN. Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio. J Clin Invest 1997, 99(8):2005-2019. 10.1172/JCI119369, 508026, 9109446.
25. Boemi M, Leviev I, Sirolla C, Pieri C, Marra M, James RW. Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation. Atherosclerosis 2001, 155(1):229-235. 10.1016/S0021-9150(00)00556-6, 11223446.
26. Garin MC, Kalix B, Morabia A, James RW. Small, dense lipoprotein particles and reduced paraoxonase-1 in patients with the metabolic syndrome. J Clin Endocrinol Metab 2005, 90(4):2264-2269. 10.1210/jc.2004-1295, 15687341.
27. Ansell BJ, Navab M, Hama S, Kamranpour N, Fonarow G, Hough G, Rahmani S, Mottahedeh R, Dave R, Reddy ST. Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation 2003, 108(22):2751-2756. 10.1161/01.CIR.0000103624.14436.4B, 14638544.
28. Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. Jama 2003, 290(17):2292-2300. 10.1001/jama.290.17.2292, 14600188.
29. Navab M, Anantharamaiah GM, Reddy ST, Hama S, Hough G, Grijalva VR, Yu N, Ansell BJ, Datta G, Garber DW. Apolipoprotein A-I mimetic peptides. Arterioscler Thromb Vasc Biol 2005, 25(7):1325-1331. 10.1161/01.ATV.0000165694.39518.95, 15831812.
30. Masson P, Josse D, Lockridge O, Viguie N, Taupin C, Buhler C. Enzymes hydrolyzing organophosphates as potential catalytic scavengers against organophosphate poisoning. J Physiol Paris 1998, 92(5-6):357-362. 10.1016/S0928-4257(99)80005-9, 9789837.
31. Sogorb MA, Garcia-Arguelles S, Carrera V, Vilanova E. Serum albumin is as efficient as paraxonase in the detoxication of paraoxon at toxicologically relevant concentrations. Chem Res Toxicol 2008, 21(8):1524-1529. 10.1021/tx800075x, 18597495.
32. Josse D, Ebel C, Stroebel D, Fontaine A, Borges F, Echalier A, Baud D, Renault F, Le Maire M, Chabrieres E. Oligomeric states of the detergent-solubilized human serum paraoxonase (PON1). J Biol Chem 2002, 277(36):33386-33397. 10.1074/jbc.M200108200, 12080042.
33. Rochu D, Renault F, Clery-Barraud C, Chabriere E, Masson P. Stability of highly purified human paraoxonase (PON1): association with human phosphate binding protein (HPBP) is essential for preserving its active conformation(s). Biochim Biophys Acta 2007, 1774(7):874-883.
34. Aharoni A, Gaidukov L, Yagur S, Toker L, Silman I, Tawfik DS. Directed evolution of mammalian paraoxonases PON1 and PON3 for bacterial expression and catalytic specialization. Proc Natl Acad Sci USA 2004, 101(2):482-487. 10.1073/pnas.2536901100, 327173, 14695884.
35. Gaidukov L, Tawfik DS. High affinity, stability, and lactonase activity of serum paraoxonase PON1 anchored on HDL with ApoA-I. Biochemistry 2005, 44(35):11843-11854. 10.1021/bi050862i, 16128586.
36. Aharoni A, Gaidukov L, Khersonsky O, Mc QGS, Roodveldt C, Tawfik DS. The 'evolvability' of promiscuous protein functions. Nat Genet 2005, 37(1):73-76.
37. Gupta RD, Tawfik DS. Directed enzyme evolution via small and effective neutral drift libraries. Nat Methods 2008, 5(11):939-942. 10.1038/nmeth.1262, 18931667.
38. Presta LG. Molecular engineering and design of therapeutic antibodies. Curr Opin Immunol 2008, 20(4):460-470. 10.1016/j.coi.2008.06.012, 18656541.
39. Vellard M. The enzyme as drug: application of enzymes as pharmaceuticals. Curr Opin Biotechnol 2003, 14(4):444-450. 10.1016/S0958-1669(03)00092-2, 12943856.
40. Gan KN, Smolen A, Eckerson HW, La Du BN. Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos 1991, 19(1):100-106.
41. Billecke S, Draganov D, Counsell R, Stetson P, Watson C, Hsu C, La Du BN. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 2000, 28(11):1335-1342.
42. Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998, 101(8):1581-1590. 10.1172/JCI1649, 508738, 9541487.
43. Nichols AV, Gong EL, Blanche PJ, Forte TM. Characterization of discoidal complexes of phosphatidylcholine, apolipoprotein A-I and cholesterol by gradient gel electrophoresis. Biochim Biophys Acta 1983, 750(2):353-364.
44. Matz CE, Jonas A. Micellar complexes of human apolipoprotein A-I with phosphatidylcholines and cholesterol prepared from cholate-lipid dispersions. J Biol Chem 1982, 257(8):4535-4540.
45. Gaidukov L, Rosenblat M, Aviram M, Tawfik DS. The 192R/Q polymorphs of serum paraoxonase PON1 differ in HDL binding, lipolactonase stimulation, and cholesterol efflux. J Lipid Res 2006, 47(11):2492-2502. 10.1194/jlr.M600297-JLR200, 16914770.
46. Jayaraman S, Gantz DL, Gursky O. Effects of protein oxidation on the structure and stability of model discoidal high-density lipoproteins. Biochemistry 2008, 47(12):3875-3882. 10.1021/bi7023783, 18302337.
47. Ryan RO, Forte TM, Oda MN. Optimized bacterial expression of human apolipoprotein A-I. Protein Expr Purif 2003, 27(1):98-103. 10.1016/S1046-5928(02)00568-5, 12509990.
48. Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 2004, 11(5):412-419. 10.1038/nsmb767, 15098021.
49. Kuo CL, La Du BN. Calcium binding by human and rabbit serum paraoxonases. Structural stability and enzymatic activity. Drug Metab Dispos 1998, 26(7):653-660.
50. Kuo CL, La Du BN. Comparison of purified human and rabbit serum paraoxonases. Drug Metab Dispos 1995, 23(9):935-944.
51. Roodveldt C, Aharoni A, Tawfik DS. Directed evolution of proteins for heterologous expression and stability. Curr Opin Struct Biol 2005, 15(1):50-56. 10.1016/j.sbi.2005.01.001, 15718133.
52. O'Sullivan WJ, Smithers GW. Stability constants for biologically important metal-ligand complexes. Methods Enzymol 1979, 63:294-336. full_text, 41156.
53. Mills BJ, Lang CA. Differential distribution of free and bound glutathione and cyst(e)ine in human blood. Biochem Pharmacol 1996, 52(3):401-406. 10.1016/0006-2952(96)00241-9, 8687493.
54. Sorenson RC, Primo-Parmo SL, Kuo CL, Adkins S, Lockridge O, La Du BN. Reconsideration of the catalytic center and mechanism of mammalian paraoxonase/arylesterase. Proc Natl Acad Sci USA 1995, 92(16):7187-7191. 10.1073/pnas.92.16.7187, 41304, 7638166.
55. Gilbert HF. Thiol/disulfide exchange equilibria and disulfide bond stability. Methods Enzymol 1995, 251:8-28. 10.1016/0076-6879(95)51107-5, 7651233.
56. Muscat JE, Kleinman W, Colosimo S, Muir A, Lazarus P, Park J, Richie JP. Enhanced protein glutathiolation and oxidative stress in cigarette smokers. Free radical biology & medicine 2004, 36(4):464-470. 10.1016/j.freeradbiomed.2003.11.018, 14975449.
57. Nicholls SJ, Hazen SL. Myeloperoxidase and cardiovascular disease. Arterioscler Thromb Vasc Biol 2005, 25(6):1102-1111. 10.1161/01.ATV.0000163262.83456.6d, 15790935.
58. Panzenboeck U, Raitmayer S, Reicher H, Lindner H, Glatter O, Malle E, Sattler W. Effects of reagent and enzymatically generated hypochlorite on physicochemical and metabolic properties of high density lipoproteins. J Biol Chem 1997, 272(47):29711-29720. 10.1074/jbc.272.47.29711, 9368040.
59. Bergt C, Oettl K, Keller W, Andreae F, Leis HJ, Malle E, Sattler W. Reagent or myeloperoxidase-generated hypochlorite affects discrete regions in lipid-free and lipid-associated human apolipoprotein A-I. Biochem J 2000, 346(Pt 2):345-354. 10.1042/0264-6021:3460345, 1220859, 10677352.
60. Francis GA. High density lipoprotein oxidation: in vitro susceptibility and potential in vivo consequences. Biochim Biophys Acta 2000, 1483(2):217-235.
61. Brinton EA, Oram JF, Chen CH, Albers JJ, Bierman EL. Binding of high density lipoprotein to cultured fibroblasts after chemical alteration of apoprotein amino acid residues. J Biol Chem 1986, 261(1):495-503.
62. Shao B, Oda MN, Vaisar T, Oram JF, Heinecke JW. Pathways for oxidation of high-density lipoprotein in human cardiovascular disease. Current opinion in molecular therapeutics 2006, 8(3):198-205.
63. Calabresi L, Sirtori CR, Paoletti R, Franceschini G. Recombinant apolipoprotein A-IMilano for the treatment of cardiovascular diseases. Curr Atheroscler Rep 2006, 8(2):163-167. 10.1007/s11883-006-0054-4, 16510051.
64. Hobbiger F. Protection against the lethal effects of organophosphates by pyridine-2-aldoxime methiodide. British journal of pharmacology and chemotherapy 1957, 12(4):438-446. 1510585, 13489171.