Go to the content. | Move to the navigation | Go to the site search | Go to the menu | Contacts | Accessibility

| Create Account

Giaretta, Giulia (2008) Acidi nucleici come target terapeutici nello sviluppo di composti antivirali o antiproliferativi. [Ph.D. thesis]

Full text disponibile come:

Documento PDF

Abstract (english)

Nucleic acids represent a good target for the development of new drugs, whose mechanism of action can be related to the inhibition of nuclear functions, both through a direct interaction with DNA or RNA, or by interference with enzymatic or not enzymatic elements fundamental for the replication and transcription of the nucleic acids.
In this thesis we analyzed the activity of potential antiviral or antitumoral drugs, whose therapeutic targets are represented by viral or cellular nucleic acids, alone or in complex with proteins.
An attractive target for the development of new antiviral agents against HIV-1 is the interaction between Tat and TAR. Tat (transactivator of transcription), is a small HIV protein rich in arginines essential for viral gene expression, replication and pathogenesis. Tat requires specific interactions with TAR (trans-activation responsive region), a short RNA structure located at the 5' ends of all nascent HIV-1 transcripts. Small molecules able to interfere with TAR and to compete for Tat binding would possess antiviral activity due to inhibition of viral transcription and expression, resulting in non-assembly of mature functional virions.
The goal of our first research is the study of compounds able to interfere with the viral phase of trans-activation. To this aim we have analyzed two series of 2-phenylquinolones (series WRNA), synthesized by the group of Prof. Cecchetti and Prof. Tabarrini of the University of Perugia. These new compounds are designed rationally with the aim of binding the TAR bulge thus interfering with Tat-TAR complex formation.
To evaluate the interference toward the Tat/TAR complex of the novel quinolones, we have developed a Fluorescence Quenching assay (FQA). The FQA protocol envisages the use of a nucleic acid labelled with a quencher moiety (Q) and of a peptide labelled with a fluorescence dye (F). In particular we have used a RNA-TAR labelled with the quencher dabcyl and the sequence of the core of Tat labelled with the donor fluorescein at its N-terminal. The fluorescence is high when the macromolecule is free in solution, but emission dramatically decreases when the fluorophore is in close proximity to the quencher molecule (i.e. when the Tat-TAR complex is formed), thus allowing to quantify the extent of complex formation. With this FQ assay we have been able to study the inhibition of Tat/TAR complex formation, i.e. to discriminate the WRNA quinolones with an inhibitory activity comparable or better than the positive control WM5, from the compounds that are weaker competitors of peptide/RNA complex. The results obtained for the first serie of phenylquinolones were consistent with those obtained by gel shift analysis (EMSA): this classic electrophoresis assay confirmed the ability of some new compounds to distrupt the complex in vitro.
We have then evaluated the binding affinities of the compounds toward TAR either wild type or mutant; mutants were designed to discriminate the relative contribution to binding by the different substructures of the nucleic acid (stem, loop, bulge); an RNA sequences not related to TAR (tRNA) and DNA, both single and double strand were also analyzed. The binding affinity of the first series quinolones toward nucleic acids was evaluated by equilibrium dialysis measurements.
Finally we have estimated the antiviral activity of these basic compounds, their cytotoxicity by MTT assay and their cell penetration by uptake studies with different cell lines and protocols.
The compounds of the first series that emerged as mostly active led to the synthesis of a second series of 2-phenylquinolones. The effect of the designed substitutions on quinolone rings on activity, tested by FQ assay, cytotoxicity and cell penetration has allowed us to delineate a more precise structure-activity relationship (SAR), useful to direct further synthesis of active compounds.
The Fluorescence Quenching assay used for testing the interfering with Tat-TAR complex represent a protocol for HTS (High Throughput Screening) analysis to efficiently test library of potential inhibitors. Therefore we have tested other classes of compounds beside the WRNA series. In particular we have evaluated the activity of some of 6-aminoquinolone derivatives, a small serie of acridone derivatives and some anthraquinones with one or two peptide chains at position 2 and/or 6.
With this first screening we have been able to identify very active compounds, and have gotten further indications related to the interaction from the molecules with the RNA-TAR and the implication for Tat inhibition.
The second project aimed at cellular DNA sequences hence at possible anticancer goals, we have analyzed the sequence specificity of DNA binding of a new series of peptidyl-anthraquinones synthesized according to the modelling studies of Prof. Gresh of the University of Paris; these theoretical studies suggested that tailor made drug peptide conjugates can be properly designed to target specific base pairs arrangements.
Therefore we describe here the DNA binding characteristic and cellular activity of a series of compounds in which the planar anthraquinone chromophore fused to the side chains of ametantrone or to other bioisosteric linkers has been conjugated to simple peptidyl chains. Peculiarity of these peptide derivatives of ametantrone stands in the selective binding to important palindromic sequences, as the sequence d(CCCGGG)2, located in several oncogenes and in HIV-1 LTR.
To evaluate the intercalating power of the novel compounds, we have used the unwinding assays. Then, the attention is turned to a assay more sensitive to study the sequence specificity: by the use of appropriate FRET (Fluorescence Resonance Energy Transfer) probes devised according to modelling studies we have demonstrated the sequence-specific properties of the novel designed compounds and thus validate the theoretical predictions.
To this point, once validate the theoretical predictions about the specificity of sequence, we have estimated the effect of the new molecules on Topoisomerase II, an enzyme target of many antineoplastic agents, that acts on the DNA. Particularly we have tested two different types of enzymatic activity: the decatenation and the relaxation of the plasmid DNA.
Finally we have examined the cytotoxicity and the potentiality of the drugs to cross the cellular membranes through experimental calculation of the partition coefficient.
The results obtained by these last studies, with the encouraging data of selectivity of sequence of some compounds, give useful indications to address the synthesis of new active derivatives with high specificity toward oncogenic sequences.

Statistiche Download - Aggiungi a RefWorks
EPrint type:Ph.D. thesis
Tutor:Gatto, Barbara
Ph.D. course:Ciclo 20 > Scuole per il 20simo ciclo > SCIENZE MOLECOLARI > SCIENZE FARMACEUTICHE
Data di deposito della tesi:31 January 2008
Anno di Pubblicazione:31 January 2008
Key Words:Tat-TAR, Transattivazione, Chinoloni, Peptidil-Antrachinoni, Sequenza-specifico
Settori scientifico-disciplinari MIUR:Area 03 - Scienze chimiche > CHIM/08 Chimica farmaceutica
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Scienze Farmaceutiche
Codice ID:549
Depositato il:24 Oct 2008
Simple Metadata
Full Metadata
EndNote Format


I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

1. Levy, J. A., Hoffman, A. D., Kramer, S. M., Landis, J. A., Shimabukuro, J. M. & Oshiro, L. S. (1984) Science 225, 288-290. Cerca con Google

2. Gallo, R. C., Salahuddin, S. Z., Popovic, M., Shearer, G. M., Kaplan, M., Haynes, B. F., Palker, T. J., Redfield, R., Oleske, J. & Safai, B. (1984) Science 224, 500-503. Cerca con Google

3. Lifson, J. D., Reyes, G. R., McGrath, M. S., Stein, B. S. & Engleman, E. G. (1986) Science 232, 1123-1127. Cerca con Google

4. Hughes, A. & Corrah, T. (1990) Blood. Rev. 4, 158-164. Cerca con Google

5. Muesing, M. A., Smith, D. H. & Capon, D. J. (1987) Cell 48, 691-701. Cerca con Google

6. Bohnlein, S., Hauber, J. & Cullen, B. R. (1989) J. Virol. 63, 421-424. Cerca con Google

7. Feng, S. & Holland, C. (1988) Nature 334, 165-170. Cerca con Google

8. Dalgleish, A. G., Beverley, P. C., Clapham, P. R., Crawford, D. H., Greaves, M. F. & Weiss, R. A. (1984) Nature 312, 763-767. Cerca con Google

9. Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guetard, D., Hercend, T., Gluckman, J. C. & Montagnier, L. (1984) Nature 312, 767-768. Cerca con Google

10. Schwartzberg, P., Colicelli, J. & Goff, S. P. (1984) Cell 37, 1043-1052. Cerca con Google

11. Katoh, I., Yoshinaka, Y., Rein, A., Shibuya, M., Odaka, T. & Oroszlan, S. (1985) Virology 145, 280-292. Cerca con Google

12. De Clercq, E. (1995) Clin. Microbiol. Rev. 8, 200-239. Cerca con Google

13. Kolata, G. (1987) Science 235, 1570-1577. Cerca con Google

14. Spence, R. A., Kati, W. M., Anderson, K. S. & Johnson, K. A. (1995) Science 267, 988-993. Cerca con Google

15. Steele, F. (1995) Nat. Med. 1, 285-286. Cerca con Google

16. Bieniasz, P. D., Grdina, T. A., Bogerd, H. P. & Cullen, B. R. (1999) Mol. Cell Biol. 19, 4592-4599. Cerca con Google

17. Jeang, K. T. & Gatignol, A. (1994) Curr. Top Microbiol. Immunol. 188, 123- 144. Cerca con Google

18. Berkhout, B. & Jeang, K. T. (1992) J. Virol. 66, 139-49. Cerca con Google

19. Calnan, B. J., Biancalana, S., Hudson, D. & Frankel, A. D. (1991) Genes Dev. 5, 201-210. Cerca con Google

20. Cordingley, M. G., LaFemina, R. L., Callahan, P. L., Condra, J. H., Sardana, V. V., Graham, D. J., Nguyen, T. M., LeGrow, K., Gotlib, L. & Schlabach, A. J. (1990) Proc. Natl. Acad. Sci. U S A 87, 8985-8989. Cerca con Google

21. Berkhout, B., Gatignol, A., Silver, J. & Jeang, K. T. (1990) Nucleic Acids Res. 18, 1839-1846. Cerca con Google

22. Neuveut, C. & Jeang, K. T. (1996) J. Virol. 70, 5572-5581. Cerca con Google

23. Kuppuswamy, M., Subramanian, T. & Srinivasan, A. (1989) Nucl. Acids Res. 17, 3551-3561. Cerca con Google

24. Churcher, M., Lamont, C., Hamy, F., Dingwall, C., Green, S. M., Lowe, A. D., Butler, P., Gait, M. J. & Karn, J. (1993) J. Mol. Biol. 230, 90-110. Cerca con Google

25. Loret, E. P., Georgel, P. & Johnson, J., W. C. (1992) Proc. Natl. Acad. Sci. USA 89, 9734-9738. Cerca con Google

26. Efthymiadis, A., Briggs, L. J. & Jans, D. A. (1998) J. Biol. Chem. 273, 1623- 1628. Cerca con Google

27. Berkhout, B., Silverman, R. H. & Jeang, K. T. (1989) Cell 59, 273-282. Cerca con Google

28. Lund, L., Wahren, B. & Garcia-Blanco, M. A. (2003) J. Gen. Virol. 84, 603- 606. Cerca con Google

29. Wang, Z. & Rana, T. M. (1996) Biochemistry 35, 6491-6499. Cerca con Google

30. Wang, Z. & Rana, T. M. (1998) Biochemistry 37, 4235-4243. Cerca con Google

31. Rice, A. P. & Carlotti, F. (1990) J. Virol. 64, 6018-6026. Cerca con Google

32. Endo, S., Kubota, S., Siomi, H., Adachi, A., Oroszlan, S., Maki, M. & Hatanaka, M. (1989) Virus Genes 3, 99-110. Cerca con Google

33. Hauber, J., Malim, M. H. & Cullen, B. R. (1989) J. Virol. 63, 1181-1187. Cerca con Google

34. Tao, J. & Frankel, A. D. (1993) Proc. Natl. Acad. Sci. USA 56, 1571-1575. Cerca con Google

35. Aboul-Ela, G. K., J.; Varani, G. (1996) Nucleic Acid Res. 24, 3974-3981. Cerca con Google

36. Marciniak, R. A. & Sharp, P. A. (1991) EMBO J. 10, 4189-4196. Cerca con Google

37. Nikolov, D. B. & Burley, S. K. (1997) Proc. Natl. Acad. Sci. USA 94, 15-22. Cerca con Google

38. Herman, C. H. & Rice, A. P. (1995) J. Virol. 69, 231-236. Cerca con Google

39. Zhu, Y., Pe'ery, T., Peng, J., Ramanathan, Y., Marshall, N., Marshall, T., Amendt, B., Mathews, M. B. & Price, D. H. (1997) Genes Dev. 11, 2622-2632. Cerca con Google

40. Wei, P., Garber, M. E., Fang, S. M., Fischer, W. H. & Jones, K. A. (1998) Cell 92, 451-462. Cerca con Google

41. Rusnati, M. & Presta, M. (2002) Drugs of the Future 27, 481-493. Cerca con Google

42. Noonan, D. & Albini, A. (2000) Adv. Pharmacol. 48, 229-250. Cerca con Google

43. Albini, A. B., G.; Benelli, R. (1995) Proc. Natl. Acad. Sci. USA 92, 4838-4842. Cerca con Google

44. Barillari, G. G., R.; Gallo, R. C. (1993) Proc. Natl. Acad. Sci. USA 90, 7941- 7945. Cerca con Google

45. Vivès, E., Brodin, P. & Lebleu, B. (1997) J. Biol. Chem. 272, 16010-16017. Cerca con Google

46. Re, M. C., Furlini, G. & Vignoli, M. (1995) J. Acquir. Im. Def. Syndr. Hum.Retr. 10, 408-416. Cerca con Google

47. Zagury, D., Lachgar, A. & Chams, V. (1998) Proc. Natl. Acad. Sci. USA 95, 3851-3856. Cerca con Google

48. Cohen, S. S., Li, C. & Ding, L. (1999) Proc. Natl. Acad. Sci. USA 96, 10842- 10847. Cerca con Google

49. Huang, L. M., Chao, M. F. & Chen, M. Y. (2001) J. Biol. Chem. 276, 13427- 13432. Cerca con Google

50. Gallo, R. C. (1999) Proc. Natl. Acad. Sci. U S A 96, 8324-8326. Cerca con Google

51. Karn, J. (1999) J. Mol. Biol. 293, 235-254. Cerca con Google

52. Baba, M. (2004) Curr. Top. Med. Chem. 4, 871-883. Cerca con Google

53. Krebs, A., Ludwig, V., Boden, O. & Göbel, M. W. (2003) Chem. Bio. Chem. 4, 1125-1131. Cerca con Google

54. Kashanchi, F., Sadaie, M. R. & Brady, J. N. (1997) Virology 227, 431-440. Cerca con Google

55. Choudhury, I., Wang, J., Rabson, A. B., Stein, S., Pooyan, S. & Leibowitz, M. J. (1998) J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 17, 104-111. Cerca con Google

56. Hamy, F., Felder, E. R., Heizmann, G., Lazdins, J., Aboul-ela, F., Varani, G., Karn, J. & Klimkait, T. (1997) Proc. Natl. Acad. Sci. USA 94, 3548-3553. Cerca con Google

57. Tamilarasu, N., Zhang, J., Hwang, S. & Rana, T. M. (2001) Bioconjug. Chem. 12, 135-138. Cerca con Google

58. Lee, C. W., Cao, H., Ichiyama, K. & Rana, T. M. (2005) Bioorg. Med. Chem. Lett. 15, 4243-4246. Cerca con Google

59. Chuah, M. K., Vandendriessche, T., Chang, H. K., Ensoli, B. & Morgan, R. A. (1994) Hum. Gene Ther. 5, 1467-1475. Cerca con Google

60. Boulme, F., Perala-Heape, M., Sarih-Cottin, L. & Litvak, S. (1997) Biochim.Biophys. Acta 1351, 249-255. Cerca con Google

61. Puerta-Fernandez, E., Barroso-del Jesus, A., Romero-Lopez, C., Tapia, N., Martinez, M. A. & Berzal-Herranz, A. (2005) Aids 19, 863-870. Cerca con Google

62. Puerta-Fernandez, E., Romero-Lopez, C., Barroso-delJesus, A. & Berzal- Herranz, A. (2003) FEMS Microbiol. Rev. 27, 75-97. Cerca con Google

63. Darfeuille, F., Hansen, J. B., Orum, H., Di Primo, C. & Toulme, J. J. (2004) Nucleic. Acids Res. 32, 3101-3107. Cerca con Google

64. Darfeuille, F., Arzumanov, A., Gryaznov, S., Gait, M. J., Di Primo, C. & Toulme, J. J. (2002) Proc. Natl. Acad. Sci. U S A 99, 9709-9714. Cerca con Google

65. Kolb, G., Reigadas, S., Boiziau, C., van Aerschot, A., Arzumanov, A., Gait, M. J., Herdewijn, P. & Toulme, J. J. (2005) Biochemistry 44, 2926-2933. Cerca con Google

66. Li, M. J., Bauer, G., Michienzi, A., Yee, J. K., Lee, N. S., Kim, J., Li, S., Castanotto, D., Zaia, J. & Rossi, J. J. (2003) Mol. Ther. 8, 196-206. Cerca con Google

67. Martinez, M. A., Gutierrez, A., Armand-Ugon, M., Blanco, J., Parera, M., Gomez, J., Clotet, B. & Este, J. A. (2002) Aids 16, 2385-2390. Cerca con Google

68. Nifosi, R., Reyes, C. M. & Kollman, P. A. (2000) Nucl. Acids Res. 28, 4944- 4955. Cerca con Google

69. Faber, C., Sticht, H., Schweimer, K. & Roesh, P. (2000) J. Biol. Chem. 275, 20660-20666. Cerca con Google

70. DeLano, W. L. (2002) Curr. Opin. Struct. Biol. 12, 14-20. Cerca con Google

71. Ippolito, J. & Steitz, T. A. (1998) Proc. Natl. Acad. Sci. USA 95, 9819-9824. Cerca con Google

72. Al-Hashimi, H. M. G., Y.; Gorin, A.; Hu, W.; Majumdar, A.; Patel, D. J. (2002) J. Mol. Biol. 315, 95-102. Cerca con Google

73. Brodsky, A. S. E., H.; Williamson, J. R. (1998) Nucleic Acids Res. 26, 1991- 1995. Cerca con Google

74. Bailly, C., Colson, P., Houssier, C. & Hamy, F. (1996) Nucleic Acids Res. 24, 1460-1464. Cerca con Google

75. Dassonneville, L., Hamy, F., Colson, P., Houssier, C. & Bailly, C. (1997) Nucleic Acids Res. 25, 4487-4492. Cerca con Google

76. Peytou, V., Condom, R., Patino, N., Guedj, R., Aubertin, A. M., Gelus, N., Bailly, C., Terreux, R. & Cabrol-Bass, D. (1999) J. Med. Chem. 42, 4042-4053. Cerca con Google

77. Gelus, N. H., F.; Bailly, C. (1999) Bioorg. Med. Chem. 7, 1075-1079. Cerca con Google

78. Hamy, F., Brondani, V., Flörsheimer, A., Stark, W., Blommers, M. J. & Klimkait, T. (1998) Biochemistry 37, 5085-5095. Cerca con Google

79. Murchie, A. I., Davis, B., Isel, C., Afshar, M., Drysdale, M. J., Bower, J., Potter, A. J., Starkey, I. D., Swarbrick, T. M., Mirza, S., Prescott, C. D., Vaglio, P., Aboul-ela, F. & Karn, J. (2004) J. Mol. Biol. 336, 625-638. Cerca con Google

80. Murchie, A. I. H., Davis, B., Afshar, M., Drysdeale, M. J., Bower, J., Potter, J., Starkey, I. D., Swarbrick, T. M., Aboul-Ela, F., Karn, J., Varani, G. & Lentzen, G. (2004) J. Mol. Biol. 336, 343-356. Cerca con Google

81. Palumbo, M., Gatto, B., Zagotto, G. & Palu, G. (1993) Trends Microbiol. 1, 232-235. Cerca con Google

82. Palù, G., Valisena, S., Ciarrocchi, G., Gatto, B. & Palumbo, M. (1992) Proc. Natl. Acad. Sci. USA 89, 9671-9675. Cerca con Google

83. Baba, M., Okamoto, M., Kimura, Y., Ikeuchi, T., Sakaguchi, T. & Okamoto, T. (1997) Antimicrob. Agent Chemother. 41, 1250-1255. Cerca con Google

84. Baba, M., Okamoto, M., Kawamura, M., Makino, M., Higashida, T., Takashi, T., Kimura, Y., Ikeuchi, T., Tetsuka, T., Okamoyo, T. (1998) Mol. Pharmacol. 53, 1097-1103. Cerca con Google

85. Sissi, C., Andreolli, M., Cecchetti, V., Fravolini, A., Gatto, B. & Palumbo, M. (1998) Bioorg. Med. Chem. 6, 1555-1561. Cerca con Google

86. Cecchetti, V., Parolin, C., Moro, S., Pecere, T., Filipponi, E., Calistri, A., Tabarrini, O., Gatto, B., Palumbo, M., Fravolini, A. & Palu, G. (2000) J. Med. Chem. 43, 3799-3802. Cerca con Google

87. Parolin, C., Gatto, B., Del Vecchio, C., Pecere, T., Tramontano, E., Cecchetti, V., Fravolini, A., Masiero, S., Palumbo, M. & Palù, G. (2003) Antimicrob. Agents Chemother. 47, 889-896. Cerca con Google

88. Richter, S., Gatto, B., Tabarrini, O., Fravolini, A. & Palumbo, M. (2005) Bioorg. Med. Chem. Lett. 15, 4247–4251. Cerca con Google

89. Tabarrini, O., Stevens, M., Cecchetti, V., Sabatini, S., Dell'Uomo, M., Manfroni, G., Palumbo, M., Pannecouque, C., De Clercq, E. & Fravolini, A. (2004) J. Med. Chem. 47, 5567-5578. Cerca con Google

90. Richter, S., Parolin, C., Gatto, B., Del Vecchio, C., Fravolini, A., Palù, G. & Palumbo, M. (2004) Antimicrob. Agents Chemother. 48, 1895-1899. Cerca con Google

91. Forster, T. (1948) Ann. Phys. 2, 55-75. Cerca con Google

92. Haugland, R. P., Yguerabide, J. & Stryer, L. (1969) Proc. Natl. Acad. Sci. USA 63. Cerca con Google

93. Marras, S. A. (2006) M. M. B. 35, 4-16. Cerca con Google

94. Lakowicz, J. R. (2006) Principle of Flourescence Spectroscopy. Cerca con Google

95. Peelmann, F., Couturier, C., Dam, J., Zebeau, L., Tavernier, J. & Jockers, R. (2006) Trends Pharmacolog. Sci. 27, 218-25. Cerca con Google

96. Higuchi, R., Dollinger, G., Walsh, P. S. & Griffith, R. (1992) Bio-Technology 10, 413-417. Cerca con Google

97. Liu, J. & Lu, Y. (2006) Methods Mol. Biol. 335. Cerca con Google

98. Mergny, J. L. & Maurizot, J. C. (2001) Chembiochem 2, 124-32. Cerca con Google

99. Cao, H., Tamilarasu, N. & Rana, T. M. (2006) Bioconjug. Chem. 17, 352-358. Cerca con Google

100. Tao, J. & Frankel, A. D. (1992) Proc. Natl. Acad. Sci. USA 89, 2723-2726. Cerca con Google

101. Boyle, P. & Ferlay, J. (2005) Ann. Oncol. 2005 16, 481-488. Cerca con Google

102. Gasser, S. & Raulet, D. (2006) Seminars in Cancer Biology Natural killer cells in cancer 2006 16. Cerca con Google

103. Kiaris, H. (2006) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim: 2006, 188. Cerca con Google

104. Krapcho, A. P., Gaetahun, Z., Avery, K. L., Hacker, M. P., Spinelli, S. & Pezzoni, G. (1991) J. Med. Chem. 34, 2373-80. Cerca con Google

105. Morreal, C. E., Bernacki, R. J., Hillman, M., Atwood, A. & Certonia, D. (1990) J. Med. Chem. 33, 490-492. Cerca con Google

106. Murray, J. T. (2006) Expert. Opin. Drug. Saf. 5, 265-74. Cerca con Google

107. Lerman, L. S. (1961) J. Mol. Biol. 3, 18-30. Cerca con Google

108. Chen, K. X., Gresh, N. & Pullmann, B. (1986) Nucleic Acid. Res. 14, 9103. Cerca con Google

109. Gatto, B., Capranico, G. & Palumbo, M. (1999) Curr. Pharm. Des. 5, 195-215. Cerca con Google

110. Fisher, G. R., Brown, J. R. & Patterson, L. H. (1990) Free Radical Res. Commun. 11, 117-125. Cerca con Google

111. Blanz, J., Mewes, K., Ehninger, G., Proksch, B., Waidelich, D., Grager, B. & Zeller, K. P. (1991) Drug Metab. Dispos., 871-880. Cerca con Google

112. Kolodziejczyk, P., Reszka, K. & Lown, J. W. (1988) Free Radical Biol. Med. 5, 13-25. Cerca con Google

113. Murdock, K. C., Child, R. G., Fabio, P. F., Angier, R. B., Wallace, R. E., Durr, F. E. & Citarella, R. V. (1979) J. Med. Chem. 22, 1024-30. Cerca con Google

114. Palumbo, M., Gatto, B., Moro, S., Sissi, C. & Zagotto, G. (2002) Biochim. Biphys. Acta 1587. Cerca con Google

115. Zagotto G., U. E., Antonello C., Conconi M.T., Marciani Magno S. (1992) Med. Chem. Lett. 2, 659-662. Cerca con Google

116. Gatto B., Z. G., Sissi, C., Cera, C., Uriarte, E., Palù, G., Palumbo, M. (1995) J. Med. Chem. 39. Cerca con Google

117. Pullman, B. (1991) Anticancer Drug Des. 6, 95-105. Cerca con Google

118. Hui, X. W., Gresh, N. & Pullman, B. (1990) Nucleic Acids Res. 18, 1109-14. Cerca con Google

119. Dervan, P. B. (2001) Bioorganical and Medicinal Chemistry 9, 2215. Cerca con Google

120. Arcamone, F. (1981) Academic Press: New York. Cerca con Google

121. Bourdouxhe-Housiaux, C. C., Houssier, C., Waring, M. J. & Bailly, C. (1996) Biochemistry 35, 4251. Cerca con Google

122. Far, S. K., Verchere-Beaur, C., Gresh, N., Taillandier, E. & Perree-Fauvet, M. (2004) Eur. J. Org. Chem., 1781. Cerca con Google

123. Gresh, N. & Kahn, P. (1991) J. Biomol. Struct. Dyn. 8, 827-845. Cerca con Google

124. Dvorak, M., Urbanek, Bartunek, P., Paces, V., Vlach, J., Pecenka, V. & Arnold, L. (1989) Nucleic Acids Res. 17, 458-466. Cerca con Google

125. Burnouf, D., Koehl, P. & Fuchs, R. P. (1989) Proc. Nacl. Acad. Sci. 86, 4147- 51. Cerca con Google

126. Wain-Hobson S., S. P., Danos O., Cole S., Alizon M. (1985) Cell 40, 9-17. Cerca con Google

127. Muesing, M., Smith, D., Cabradilla, C., Benton, C., Lasky, L. & Capon, D. (1985) Nature 313, 450. Cerca con Google

128. Van Straaten F., M. R., Curran T., Van Beveren C., Verma I.M. (1983) Proc. Natl. Acad. Sci. U S A 80, 3183-7. Cerca con Google

129. Tsimanis A., B., Dreilina D., Meldrais J., Lozha V., Kukaine R. (1983) Nucleic Acids Res. 11, 1009-1017. Cerca con Google

130. Hong, F., Huang, H., To, H., Yuong, L., Oro, A., Bookstein, R. & Lee, W. (1989) Proc. Nat. Acad. Sci. USA 86, 5502-5509. Cerca con Google

131. Gresh, N. & Kahn, P. (1990) J. Biomol. Struct. Dyn. 7, 1141-1160. Cerca con Google

132. Butler, M. A., Matney, T. S. & Loo, T. L. (1981) Cancer. Res. 41, 376-379. Cerca con Google

133. Crick, F. H. (1976) Proc. Natl. Acad. Sci. USA 8, 2639-2643. Cerca con Google

134. S. A. Marras, F. R. Kramer & Tyagi, S. (2002) Nucleic Acid Res. 30, 1-8. Cerca con Google

135. Ratner, L., Haseltine, W., Patarca, R., Livak, K. J., Starcich, B., Josephs, S. F., Doran, E. R., Rafalski, J. A., Whitehorn, E. A. & Baumeister, K. (1985) Nature 313, 277-279. Cerca con Google

136. Pascual, A., Garcia, I. & Perea, E. (1989) Antimicrob. Agents Chemother. 33, 653-656. Cerca con Google

137. Pascual, A., Garcia, I., Ballesta, S. & Perea, E. (1999) Antimicrob. Agents Chemother. 43, 12-15. Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record