Inhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5' -end lipophilic modification

• Autorzy: Kobylanska A. , Pluskota E. , Swiatkowska M. , Wojcik M. , Cierniewska-Cieslak A. , Krakowiak A. , Boczkowska M. , Pawlowska Z. , Okruszek A. , Koziolkiewicz M. , Cierniewski C.S. , Stec W.J.
• Języki publikacji: EN

Abstrakty

EN

A series of conjugates containing residues of lipophilic alcohols covalently bound to 5'-end of oligodeoxyribonucleotides targeted against human plasminogen activator inhibitor (PAI-1) mRNA was synthesized via the oxathiaphospholane approach. The highest anti-PAI-1 activity in EA.hy 926 endothelial cell cultures was found for conjugates containing menthyl or heptadecanyl groups linked with an oligonucleotide complementary to a segment of human PAI-1 mRNA. The phosphodiester antisense oligonucleotides, which otherwise exhibit only limited anti-PAI-1 activity, were found to be more active than phosphorothioate oligonucleotides when conjugated to lipophilic alcohol residues. For menthyl conjugates an evidence of antisense mechanism of inhibition was found.

Słowa kluczowe

EN

oligodeoxyribonucleotide; plasminogen activator inhibitor; lipophilic alcohol; human plasminogen; oligonucleotide conjugate; antisense inhibition

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1999
• Tom: 46
• Numer: 3
• Opis fizyczny: p.679-691,fig.

Twórcy

autor

Kobylanska A.

• Polish Academy of Sciences, H.Sienkiewicza 112, 90-363 Lodz, Poland

autor

Pluskota E.

autor

Swiatkowska M.

autor

Wojcik M.

autor

Cierniewska-Cieslak A.

autor

Krakowiak A.

autor

Boczkowska M.

autor

Pawlowska Z.

autor

Okruszek A.

autor

Koziolkiewicz M.

autor

Cierniewski C.S.

autor

Stec W.J.

Bibliografia

• 1. Cierniewski, C.S., Babińska, A., Świątkowska, M., Wilczyńska, M., Okruszek, A. & Stec, W.J. (1995) Comparative inhibition of PAI-1 ex­pression in human endothelial cells by modi­fied oligodeoxyribonucleotides. Eur. J. Bio- chem. 227, 494-499.
• 2. Cierniewski, C.S., Pluskota. E., Krzeslowska, J., Fijałkowska, I., Kobylańska, A., Ko- ziołkiewicz, M., Okruszek, A. & Stec, W.J. (1995) Inhibition by modified oligodeoxy­ribonucleotides of the expression of the type 1 plasminogen activator inhibitor in human en­dothelial cells. Thromb. Haemost. 73, 1007.
• 3. Krishnamurti, C. & Alving, B.M. (1992) Plas­minogen activator inhibitor type 1: Biochemis­try and evidence for modulation of fibrinolysis in vivo. Semin. Thromb. HaemosL 18,67-80.
• 4. Van Meijer, M. & Pannekoek, H. (1995) Struc­ture of plasminogen activator inhibitor 1 (PAI-1) and its function in fibrinolysis: An up­date. Fibrinolysis 9, 261-276.
• 5. Stec, W.J. & Wilk, A. (1994) Stereocontrolled synthesis of oligo(nucleoside phosphorothio- ate)s. Angew. Chem. Int. Ed EngL 33, 709- 722.
• 6. Stec, W.J., Ciemiewski, C.S., Okruszek, A., Kobylańska, A., Pawłowska, Z., Koziołkiewicz, M., Pluskota, E., Maciaszek, A., Rębowska, B. & Stasiak, M. (1997) Stereodependent inhibi­tion of plasminogen activator inhibitor type 1 by phosphorothioate oligonucleotides; Proof of sequence specificity in cell culture and in vivo rats experiments. Antisense Nucleic Acids Drug Dev. 7, 567-573.
• 7. Wickstrom, E. (1986) Oligodeoxynucleotide stability in subcellular extracts and culture media. Biochem. Biophys. Metłu 13, 97-102.
• 8. Fisher, T.L., Terhorst, T., Cao, X. & Wagner, R.W. (1993) Intracellular disposition and me­tabolism of fluorescently-labeled unmodified and modified oligonucleotides microinjected into mammalian cells. Nucleic Acids Res. 21, 3857-3805.
• 9. Beaucage, S.L. & Iyer, R.P. (1992) Advances in the synthesis of oligonucleotides by phos- phoramidite approach. Tetrahedron 48,2223- 2311.
• 10. Stec, W.J., Uznański, B., Wilk, A., Hirschbein, B.L., Fearon, K.L. & Bergot, B.J. (1993) Bis- (0,0diisopropoxy phosphinothioyl)disulfide — highly efficient sulfurizing reagent for cost- effective synthesis of oligo(nucleoside phos- phorothioate)s. Tetrahedron Lett. 34, 5317- 5320.
• 11. Brown, T. & Pritchard, C.E. (1989) A new base-stabile linker for solid-phase oligonucleo­tide synthesis. J. Chem. Soc., Chem. Commun. 891-893.
• 12. Jaschke, A.. Fiirste, J.P., Nordhoff, E., Hil- lenkamp, F., Cech, D. & Erdmann, W A. (1994) Synthesis and properties of oligodeoxy- ribonucleotide-polyethylene glycol conjugates. Nucleic Acids Res. 22, 4810-4817.
• 13. Jaschke, A., Bald, R., Nordhoff, E., Hillenkamp, F., Cech, D., Erdmann, BA. & Fiirste, J.P. (1996) Synthesis and analytical characterization of RNA-polyethylene glycol conjugates. Nucleosides & Nucleotides 15, 1519-1529.
• 14. Kobylańska, A., Okruszek, A. & Stec, W.J. (1998) Application of oxathiaphospholane method for the synthesis of oligodeoxyribo- nucleotide 5'-0-conjugates. Nucleosides Nu­cleotides 17, 1977-1982.
• 15. Błaszczyk, J.f Wieczorek, M.W., Okruszek, A., Sierzchała, A., Kobylańska, A. & Stec, W.J. (1996) The synthesis and X-ray structural studies of 2-cholesteryl-2-thio-l,3,2-oxathia- phospholane and 2-cholesteryl-2-thio-l,3,2-di- thiaphospholane. J. Chem. CrysL 26, 33-42.
• 16. Stec, W.J., Grajkowski, A., Koziołkiewicz, M. & Uznański, B. (1991) Novel route to oligo- (deoxyribonucleo8ide phosphorothioates). Ste­reocontrolled synthesis of P-chiral oligo (deoxyribonucleoside phosphorothioates). Nu­cleic Acids Res. 19, 5883-5888.
• 17. Stec, W.J., Grajkowski, A., Kobylańska, A., Koziołkiewicz, M., Misiura, K., Okruszek, A., Wilk, A., Guga, P. & Boczkowska, M. (1995) Diastereomers of nucleoside 3'-
• 18. Levin, E.G. (1986) Quantitation and proper­ties of the active and latent plasminogen acti­vator inhibitors in cultures of human endothe­lial cells. Blood 67, 1309-1313.
• 19. Lewis, M.L., Nachtway, D.S. & Damron, K.L. (1991) A miniaturized fibrinolytic assay for plasminogen activators. Thromb. Res. 64, 223-234.
• 20. Goodchild, J. (1990) Conjugates of oligo­nucleotides and modified oligonucleotides: A review of their synthesis and properties. Bioconjug. Chem. 1, 165-187.
• 21. Manoharan, M. (1993) Designer antisense oligonucleotides: Conjugation chemistry and functionality placement; in Antisense Research and Applications (Crooke, S.T. & Lebleu, B., eds.) pp. 303-349, CRC Press, Boca Raton, FL.
• 22. Ramirez, F., Mandal, S.B. & Marecek, J.F. (1982) Nucleotidophospholipids: Oligonucleo­tide derivatives with membrane-recognition groups. J. Am. Chem. Soc. 104, 5483-5486.
• 23. Habus, I., Zhao, Q. & Agrawal, S. (1995) Syn­thesis, hybridization properties, nuclease sta­bility, and cellular uptake of the oligo- nucleotide-amino-cyclodextrins and adaman- tane conjugates. Bioconjug. Chem. 6,327-331.
• 24. MacKellar, C., Graham, D., Will. D.W., Bur­gess, S. & Brown, T. (1992) Synthesis and physical properties of anti-HIV antisense oligonucleotides bearing terminal lipophilic groups. Nucleic Acids Res, 20, 3411-3417.
• 25.Ortigao, J.F., Ruck, A., Gupta, K.C., Rosch, R., Steiner, R. & Seliger, H. (1993) Solid-phase in­troduction and intracellular photoinduced re­action of waier-soluble meso-tetracarboxypor- phine conjugated to an antisense oligo-deoxy- ribonucleotide. Biochimie 76, 29-34.
• 26. Boiziau, C. & Toulme, J.-J. (1991) Modified oligonucleotides in rabbit reticulocytes: Uptake, stability and antisense properties. Biochimie 73, 1403-1408.
• 27. Leonetti, J.P., Raynier, B., Lemaitre, M., Gagnor, C., Milhaud, P.G., Imbach, J.-L. & Lebleu, B. (1988) Antiviral activity of conju­gates between poly(L-lysine) and synthetic oligodeoxyribo-nucleotides. Gene 72, 323- 332.
• 28. Kuyl-Yeheskiely, E., Dreef-Tromp, C.M., Geluk, A., van der Marel, G.A. & van Boom, J.H. (1989) Synthesis of the nucleopeptides H-Phe-TyKpGONHg and H-Phe-SeKpGC> Ala-OH via a phosphotriester approach. Nu­cleic Acids Res. 17, 2897-2905.
• 29. Letsinger, R.L., Zhang, G.R, Sun, D.K., Ikeuchi, T. & Sarin, P.S. (1989) Cholesteryl- conjugated oligonucleotides: Synthesis, prop­erties, and activity as inhibitors of replication of human immunodeficiency virus in cell cul­ture. Proc. Natl Acad. ScL U.S.A. 86, 6553- 8556.
• 30. Krieg, A.M., Tonkinson, J., Matson, S., Zhao, Q., Saxon, M., Zhang, L.M., Bhanja, U., Yakubov, L. & Stein, C.A. (1993) Modification of antisense phosphodiester oligodeoxynucleo- tides by a 5' cholesteryl moiety increases cellu­lar association and improves efficacy. Proc. NatL Acad. Sci. U.S.A. 90, 1048-1052.
• 31. Stein, C.A., Pal, R., Devico, A.L., Hoke, G., Mumbauer, S., Kinstler, O., Sarngadharan, M.G. & Letsinger, R.L. (1991) Mode of action of 5'-linked cholesteryl phosphorothioate oiigodeoxynucleotides in inhibiting syncytia formation and infection by HIV-1 and HIV-2 in vitro. Biochemistry 30, 2439-2444.
• 32. Agatsuma, T., Yamamoto, I., Furukawa, H. & Nishigaki, T. (1996) Guanine-rich oligonucleo­tide modified at the 5' terminal by dimethoxy- trityl residue inhibits HIV-1 replication by spe­cific interaction with the envelope glycopro­tein. Antiviral Res. 31, 137-148.
• 33. Kobylańska, A., Pluskota, E., Pawłowska. Z., Okruszek, A., Cierniewski, C.S. & Stec, W.J. (1999) The cytotoxicity of anti-PAI-1 oligo­nucleotides and their conjugates. Nucleosides Nucleotides 18, 1709-1710.
• 34. Eder, P.S., Devine, R.J., Dagile, J.M. & Walder, J.A. (1991) Substrate specificity and kinetics of degradation of antisense oligo­nucleotides by a 3'-exonuclease in plasma. Antisense Res. Dev. 1, 141-151.
• 35. Hardin, C.C., Corregan, M.J., Lieberman, D.V. & Brown II, B.A. (1997) Allosteric interactions between DNA strands and monovalent cations in DNA quadruplex assembly: Thermody­namic evidence for three linked association pathways. Biochemistry 36, 15428-15450.
• 36.Stein, C.A. & Cheng, Y.-C. (1993) Antisense oligonucleotides as therapeutic agents — is the bullet really magical? Science 261, 1004- 1012.
• 37. Gao, W., Han, F., Storm, C., Egan, W. & Cheng, Y. (1991) Phosphorothioate oligo­nucleotides are inhibitors of human DNA poly­merases and RNase H: Implications for anti- sense technology. MoL Pharmacol 41, 223- 229.
• 38. Stein, C.A. (1995) Does antisense exist? Na­ture Med. 1, 1119-1121.
• 39. Sen, D. & Gilbert, W. (1992) Guanine quartet structures. Methods Enzymol 211, 191-199.
• 40. Wolfe, J.L. & Goodchild, J. (1996) Modulation of tetraplex formation by chemical modifica­tion of a G4-containing phosphorothioate uligunucleutide. J. Am. Chem. Soc. 118, G301- 6302.
• 41. Fang, G. & Cech, T.R. (1993) Characterization of a G-quartet formation reaction promoted by the beta-subunit of the Oxytricha telomere- binding protein. Biochemistry 32, 11646- 11657.
• 42. Liu, Z., Frantz, J.D., Gilbert, W. & Tye, B.K. (1993) Identification and characterization of a nuclease activity specific for G4 tetrastranded DNA. Proc. Natl Acad. ScL U.S.A. 90. 3157- 3161.