A comparison of DNA cleavage by neocarzinostatin chromophore and its aglycon: Evaluating the role of the carbohydrate residue

Journal of the American Chemical Society

Volumn 119, Issue 13, 1997, Pages 2965-2972

  Myers, Andrew G ^a   Kort, Michael E ^a   Hammond, Marlys ^a  

^a California Institute of Technology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NEOCARZINOSTATIN CHROMOPHORE AGLYCON; UNCLASSIFIED DRUG; ZINOSTATIN CHROMOPHORE;

ARTICLE; DNA CLEAVAGE; DNA DETERMINATION; GEL ELECTROPHORESIS; IN VITRO STUDY; NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION;

EID: 0030925110     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9641719     Document Type: Article

References (80)

1. (a) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl. 1991, 30, 1387.
2. (b) Nucleic Acid Targeted Drug Design; Propst, C. L., Perun, T. J., Eds.; Marcel Dekker: New York, 1992.
3. (c) Murphy, J. A.; Griffiths, J. Nat. Prod. Rep. 1993, 10, 551.
4. The enediyne antibiotic dynemicin A is a notable exception. For leading references, see: (a) Myers, A. G.; Fraley, M. E.; Tom, N. J.; Cohen, S. B.; Madar, D. J. Chem. Biol. 1995, 2, 33. (b) Myers, A. G.; Cohen, S. B.; Tom, N. J.; Madar, D. J.; Fraley, M. E. J. Am. Chem. Soc. 1995, 117, 7574.
5. The enediyne antibiotic dynemicin A is a notable exception. For leading references, see: (a) Myers, A. G.; Fraley, M. E.; Tom, N. J.; Cohen, S. B.; Madar, D. J. Chem. Biol. 1995, 2, 33. (b) Myers, A. G.; Cohen, S. B.; Tom, N. J.; Madar, D. J.; Fraley, M. E. J. Am. Chem. Soc. 1995, 117, 7574.
6. Isolation: (a) Shoji, J. J. Antibiot. 1961, 14, 27. (b) Ishida, N.; Miyazaki, K.; Kumagai, K.; Rikimaru, M. J. Antibiot. 1965, 18, 68. Characterization: (c) Napier, M. A.; Holmquist, B.; Strydom, D. J.; Goldberg, I. H. Biochem. Biophys. Res. Commun. 1979, 89, 635. (d) Koide, Y.; Ishii, F.; Hasuda, K.; Koyama, Y.; Edo, K.; Katamine, S.; Kitame, F.; Ishida, N. J. Antibiot. 1980, 33, 342.
7. Isolation: (a) Shoji, J. J. Antibiot. 1961, 14, 27. (b) Ishida, N.; Miyazaki, K.; Kumagai, K.; Rikimaru, M. J. Antibiot. 1965, 18, 68. Characterization: (c) Napier, M. A.; Holmquist, B.; Strydom, D. J.; Goldberg, I. H. Biochem. Biophys. Res. Commun. 1979, 89, 635. (d) Koide, Y.; Ishii, F.; Hasuda, K.; Koyama, Y.; Edo, K.; Katamine, S.; Kitame, F.; Ishida, N. J. Antibiot. 1980, 33, 342.
8. Isolation: (a) Shoji, J. J. Antibiot. 1961, 14, 27. (b) Ishida, N.; Miyazaki, K.; Kumagai, K.; Rikimaru, M. J. Antibiot. 1965, 18, 68. Characterization: (c) Napier, M. A.; Holmquist, B.; Strydom, D. J.; Goldberg, I. H. Biochem. Biophys. Res. Commun. 1979, 89, 635. (d) Koide, Y.; Ishii, F.; Hasuda, K.; Koyama, Y.; Edo, K.; Katamine, S.; Kitame, F.; Ishida, N. J. Antibiot. 1980, 33, 342.
9. Isolation: (a) Shoji, J. J. Antibiot. 1961, 14, 27. (b) Ishida, N.; Miyazaki, K.; Kumagai, K.; Rikimaru, M. J. Antibiot. 1965, 18, 68. Characterization: (c) Napier, M. A.; Holmquist, B.; Strydom, D. J.; Goldberg, I. H. Biochem. Biophys. Res. Commun. 1979, 89, 635. (d) Koide, Y.; Ishii, F.; Hasuda, K.; Koyama, Y.; Edo, K.; Katamine, S.; Kitame, F.; Ishida, N. J. Antibiot. 1980, 33, 342.
10. Chromophore structure: (a) Edo, K.; Mizugaki, M.; Koide, Y.; Seto, H.; Furihata, K.; Ōtake, N.; Ishida, N. Tetrahedron Lett. 1985, 26, 331. Carbohydrate stereochemistry: (b) Edo, K.; Akiyama, Y.; Saito, K.; Mizugaki, M.; Koide, Y.; Ishida, N. J. Antibiot. 1986, 39, 1615. Chromophore stereochemistry: (c) Myers, A. G.; Proteau, P. J.; Handel, T. M. J. Am. Chem. Soc. 1988, 110, 7212. (d) Myers, A. G.; Proteau, P. J. J. Am. Chem. Soc. 1989, 111, 1146.
11. Chromophore structure: (a) Edo, K.; Mizugaki, M.; Koide, Y.; Seto, H.; Furihata, K.; Ōtake, N.; Ishida, N. Tetrahedron Lett. 1985, 26, 331. Carbohydrate stereochemistry: (b) Edo, K.; Akiyama, Y.; Saito, K.; Mizugaki, M.; Koide, Y.; Ishida, N. J. Antibiot. 1986, 39, 1615. Chromophore stereochemistry: (c) Myers, A. G.; Proteau, P. J.; Handel, T. M. J. Am. Chem. Soc. 1988, 110, 7212. (d) Myers, A. G.; Proteau, P. J. J. Am. Chem. Soc. 1989, 111, 1146.
12. Chromophore structure: (a) Edo, K.; Mizugaki, M.; Koide, Y.; Seto, H.; Furihata, K.; Ōtake, N.; Ishida, N. Tetrahedron Lett. 1985, 26, 331. Carbohydrate stereochemistry: (b) Edo, K.; Akiyama, Y.; Saito, K.; Mizugaki, M.; Koide, Y.; Ishida, N. J. Antibiot. 1986, 39, 1615. Chromophore stereochemistry: (c) Myers, A. G.; Proteau, P. J.; Handel, T. M. J. Am. Chem. Soc. 1988, 110, 7212. (d) Myers, A. G.; Proteau, P. J. J. Am. Chem. Soc. 1989, 111, 1146.
13. Chromophore structure: (a) Edo, K.; Mizugaki, M.; Koide, Y.; Seto, H.; Furihata, K.; Ōtake, N.; Ishida, N. Tetrahedron Lett. 1985, 26, 331. Carbohydrate stereochemistry: (b) Edo, K.; Akiyama, Y.; Saito, K.; Mizugaki, M.; Koide, Y.; Ishida, N. J. Antibiot. 1986, 39, 1615. Chromophore stereochemistry: (c) Myers, A. G.; Proteau, P. J.; Handel, T. M. J. Am. Chem. Soc. 1988, 110, 7212. (d) Myers, A. G.; Proteau, P. J. J. Am. Chem. Soc. 1989, 111, 1146.
14. Kim, K.-H.; Kwon, B.-M.; Myers, A. G.; Rees, D. C. Science 1993, 262, 1042.
15. (a) Beerman, T. A.; Goldberg, I. H. Biochem. Biophys. Res. Commun. 1974, 59, 1254.
16. (b) Kappen, L. S.; Napier, M. A.; Goldberg, I. H. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 1970.
17. See also: (c) Ono, Y.; Watanabe, Y.; Ishida, N. Biochim. Biophys. Acta 1966, 119, 46.
18. (d) D'Andrea, A. D.; Haseltine, W. A. Proc. Natl. Acad. Sci. U.S.A. 1978, 75, 3608.
19. (a) Kappen, L. S.; Goldberg, I. H. Biochemistry 1983, 22, 4872.
20. (b) Kappen, L. S.; Goldberg, I. H. Nucleic Acids Res. 1985, 13, 1637.
21. (c) Goldberg, I. H. Acc. Chem. Res. 1991, 24, 191.
22. Myers, A. G. Tetrahedron Lett. 1987, 28, 4493. See also ref 4c,d.
23. (a) Chin, D.-H.; Zheng, C.-h.; Costello, C. E.; Goldberg, I. H. Biochemistry 1988, 27, 8106.
24. (b) Chin, D.-H.; Goldberg, I. H. J. Am. Chem. Soc. 1993, 115, 9341.
25. (c) Myers, A. G.; Cohen, S. B.; Kwon, B.-M. J. Am. Chem. Soc. 1994, 116, 1670.
26. (a) Hatayama, T.; Goldberg, I. H.; Takeshita, M.; Grollman, A. P.; Proc. Natl. Acad. Sci. U.S.A. 1978, 75, 3603.
27. (b) Takeshita, M.; Kappen, L. S.; Grollman, A. P.; Eisenberg, M.; Goldberg, I. H. Biochemistry 1981, 20, 7599.
28. (c) Lee, S. H.; Goldberg, I. H. Biochemistry 1989, 28, 1019.
29. (a) Povirk, L. F.; Houlgrave, C. W.; Han, Y.-H. J. Biol. Chem. 1988, 263, 19263.
30. (b) Kappen, L. S.; Chen, C-Q.; Goldberg, I. H. Biochemistry 1988, 27, 4331.
31. (c) Frank, B. L.; Worth, L., Jr.; Christner, D. F.; Kozarich, J. W.; Stubbe, J.; Kappen, L. S.; Goldberg, I. H. J. Am. Chem. Soc. 1991, 113, 2271.
32. (a) Povirk, L. F.; Dattagupta, N.; Warf, B. C.; Goldberg, I. H. Biochemistry 1981, 20, 4007.
33. (b) Dasgupta, D.; Goldberg, I. H. Biochemistry 1985, 24, 6913.
34. (c) Meschwitz, S. M.; Goldberg, I. H. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 3047.
35. (d) Meschwitz, S. M.; Schultz, R. G.; Ashley, G. W.; Goldberg, I. H. Biochemistry 1992, 31, 9117.
36. (a) Galat, A.; Goldberg, I. H. Nucleic Acids Res. 1990, 18, 2093.
37. For other models of NCS chromophore binding to DNA, see: (b) Suguiyama, H.; Fujiwara, T.; Kawabata, H.; Yoda, N.; Hirayama, N.; Saito, I. J. Am. Chem. Soc. 1992, 114, 5573.
38. (c) Elbaum, D.; Schreiber, S. L. Bioorg. Med. Chem. 1994, 4, 309.
39. Gao, X.; Stassinopolis, A.; Rice, J. S.; Goldberg, I. H. Biochemistry 1995, 34, 40.
40. Myers, A. G.; Hammond, M.; Wu, Y.; Xiang, J.-N.; Harrington, P. M.; Kuo, E. Y. J. Am. Chem. Soc. 1996, 118, 10006.
41. No characterizable products are evident upon analysis of the decomposition mixture.
42. Kishi, Y.; Aratani, M.; Tanino, H.; Fukuyama, T.; Goto, T.; Inoue, S.; Sugiura, S.; Kakoi, H. J. Chem. Soc., Chem. Commun. 1972, 64.
43. Acetic acid (10% by volume) was found to stabilize the chromophore (1) and was present in thiol addition experiments with 1, but promoted the rapid decomposition of 2 in solution and was therefore omitted from reactions with this substrate. The basis for this reactivity difference could not be established conclusively, for no characterizable products were obtained from the reaction of 2 with acetic acid. This finding provides another illustration of the greater chemical sensitivity of 2 as compared to 1.
44. Myers, A. G.; Harrington, P. M.; Kwon, B.-M. J. Am. Chem. Soc. 1992, 114, 1086.
45. The yield reported for 4 (13%) is based on the assumption that the extinction coefficient is the same for 2 and 4 at 240 nm.
46. 1 in the presence of GSH (Myers, A. G.; Cohen, S. B.; Kwon, B.-M. J. Am. Chem. Soc. 1994, 116, 1255).
47. 32P-labeled 193-base pair restriction fragment using a nondenaturing electrophoretic assay (data not shown). Consistent with the generally attenuated cleavage efficiency observed for 2 relative to 1, only traces of double-stranded cleavage by 2 (in the presence of apo-NCS) were detected. The efficiency of double-stranded DNA cleavage by 1 is at least 2-3 orders of magnitude greater than that of 2. These findings also held true in the case of piperidine treatment (1 M piperidine, 90°C, 30 min) of the cleavage products: (a) Poon, R.; Beerman, T. A.; Goldberg, I. H. Biochemistry 1977, 16, 486. (b) Dedon, P. C.; Goldberg, I. H. J. Biol. Chem. 1990, 265, 14713. (c) Kappen, L. S.; Goldberg, I. H. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 6706.
48. 32P-labeled 193-base pair restriction fragment using a nondenaturing electrophoretic assay (data not shown). Consistent with the generally attenuated cleavage efficiency observed for 2 relative to 1, only traces of double-stranded cleavage by 2 (in the presence of apo-NCS) were detected. The efficiency of double-stranded DNA cleavage by 1 is at least 2-3 orders of magnitude greater than that of 2. These findings also held true in the case of piperidine treatment (1 M piperidine, 90°C, 30 min) of the cleavage products: (a) Poon, R.; Beerman, T. A.; Goldberg, I. H. Biochemistry 1977, 16, 486. (b) Dedon, P. C.; Goldberg, I. H. J. Biol. Chem. 1990, 265, 14713. (c) Kappen, L. S.; Goldberg, I. H. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 6706.
49. 32P-labeled 193-base pair restriction fragment using a nondenaturing electrophoretic assay (data not shown). Consistent with the generally attenuated cleavage efficiency observed for 2 relative to 1, only traces of double-stranded cleavage by 2 (in the presence of apo-NCS) were detected. The efficiency of double-stranded DNA cleavage by 1 is at least 2-3 orders of magnitude greater than that of 2. These findings also held true in the case of piperidine treatment (1 M piperidine, 90°C, 30 min) of the cleavage products: (a) Poon, R.; Beerman, T. A.; Goldberg, I. H. Biochemistry 1977, 16, 486. (b) Dedon, P. C.; Goldberg, I. H. J. Biol. Chem. 1990, 265, 14713. (c) Kappen, L. S.; Goldberg, I. H. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 6706.
50. The rate of activation of 1 by GSH is known to be slower than with MTG: Dedon, P. C.; Goldberg, I. H. Biochemistry 1992, 31, 1909.
51. (a) Sugiyama, H.; Yamashita, K.; Nishi, M.; Saito, I. Tetrahedron Lett. 1992, 33, 515.
52. (b) Sugiyama, H.; Yamashita, K.; Fujiwara, T.; Saito, I. Tetrahedron 1994, 50, 1311.
53. Myers, A. G.; Arvedson, S. P.; Lee, R. W. J. Am. Chem. Soc. 1996, 118, 4725.
54. (a) Kappen, L. S.; Napier, M. A.; Goldberg, I. H. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 1970.
55. (b) Koide, Y.; Ito, A.; Ishii, F.; Koyama, Y.; Edo, K.; Ishida, N. J. Antibiot. 1982, 35, 766.
56. -1, corresponding to a half-life of ∼0.03 s. (a) Povirk, L. F.; Goldberg, I. H. Biochemistry 1980, 19, 4773. (b) Dasgupta, D.; Auld, D. S.; Goldberg, I. H. Biochemistry 1985, 24, 7049.
57. -1, corresponding to a half-life of ∼0.03 s. (a) Povirk, L. F.; Goldberg, I. H. Biochemistry 1980, 19, 4773. (b) Dasgupta, D.; Auld, D. S.; Goldberg, I. H. Biochemistry 1985, 24, 7049.
58. Electrospray mass spectroscopy of aqueous solutions of 2 containing excess apo-NCS (18 equiv) was found to produce ions consistent with a 1:1 complex of 2 and apo-NCS while all attempts to obtain a mass spectrum of 2 in isolation were unsuccessful.
59. Goldberg and co-workers have previously shown that holo-NCS (1·apo-NCS) efficiently cleaves double-stranded DNA at 37°C (ref 7c).
60. Kinetic monitoring of DNA cleavage reactions conducted at 2°C with 1 and 2 in the presence of apo-NCS (1.8 equiv) showed a slow but real increase in DNA cleavage as a function of time.
61. The nature of the thiol cofactor is known to influence the extent of bistranded DNA lesions (ref 11b) and the partitioning of the chemistry of deoxyribose damage: (a) Saito, I.; Kawabata, H.; Fujiwara, T.; Sugiyama, H.; Matsuura, T. J. Am. Chem. Soc. 1989, 111, 8302. (b) Dedon, P. C.; Jiang, Z.-W.; Goldberg, I. H. Biochemistry 1992, 31, 1917 and references cited therein. (c) Kappen, L. S.; Goldberg, I. H.; Frank, B. L.; Worth, L., Jr.; Christner, D. F.; Kozarich, J. W.; Stubbe, J. Biochemistry 1991, 30, 2034.
62. The nature of the thiol cofactor is known to influence the extent of bistranded DNA lesions (ref 11b) and the partitioning of the chemistry of deoxyribose damage: (a) Saito, I.; Kawabata, H.; Fujiwara, T.; Sugiyama, H.; Matsuura, T. J. Am. Chem. Soc. 1989, 111, 8302. (b) Dedon, P. C.; Jiang, Z.-W.; Goldberg, I. H. Biochemistry 1992, 31, 1917 and references cited therein. (c) Kappen, L. S.; Goldberg, I. H.; Frank, B. L.; Worth, L., Jr.; Christner, D. F.; Kozarich, J. W.; Stubbe, J. Biochemistry 1991, 30, 2034.
63. The nature of the thiol cofactor is known to influence the extent of bistranded DNA lesions (ref 11b) and the partitioning of the chemistry of deoxyribose damage: (a) Saito, I.; Kawabata, H.; Fujiwara, T.; Sugiyama, H.; Matsuura, T. J. Am. Chem. Soc. 1989, 111, 8302. (b) Dedon, P. C.; Jiang, Z.-W.; Goldberg, I. H. Biochemistry 1992, 31, 1917 and references cited therein. (c) Kappen, L. S.; Goldberg, I. H.; Frank, B. L.; Worth, L., Jr.; Christner, D. F.; Kozarich, J. W.; Stubbe, J. Biochemistry 1991, 30, 2034.
64. This proposal was previously set forth (ref 9c) on the basis of an analysis of the estimated rate constants for hydrogen atom abstraction by the biradical intermediate and on/off rates for the binding of such an intermediate to DNA (ref 27). Even considering the important recent findings of Chen et al., in which the rate of hydrogen atom abstraction by a biradical such as B is revised downward, the rate of such a hydrogen atom abstraction is still estimated to be faster than equilibration of the biradical with another site of intercalation: (a) Logan, C. F.; Chen, P. J. Am. Chem. Soc. 1996, 118, 2113. (b) Schottelius, M. J.; Chen, P. J. Am. Chem. Soc. 1996, 118, 4896.
65. This proposal was previously set forth (ref 9c) on the basis of an analysis of the estimated rate constants for hydrogen atom abstraction by the biradical intermediate and on/off rates for the binding of such an intermediate to DNA (ref 27). Even considering the important recent findings of Chen et al., in which the rate of hydrogen atom abstraction by a biradical such as B is revised downward, the rate of such a hydrogen atom abstraction is still estimated to be faster than equilibration of the biradical with another site of intercalation: (a) Logan, C. F.; Chen, P. J. Am. Chem. Soc. 1996, 118, 2113. (b) Schottelius, M. J.; Chen, P. J. Am. Chem. Soc. 1996, 118, 4896.
66. (a) Barton, J. K. Science 1986, 233, 727.
67. (b) Pyle, A. M.; Mori, T.; Barton, J. K. J. Am. Chem. Soc. 1990, 112, 9432.
68. (c) Sitlani, A.; Long, E. C.; Pyle, A. M.; Barton, J. K. J. Am. Chem. Soc. 1992, 114, 2303.
69. See also: (d) Dickerson, R. E.; Drew, H. R. J. Mol. Biol. 1981, 149, 761.
70. (a) Zein, N.; Poncin, M.; Nilakantan, R.; Ellestad, G. A. Science 1989, 244, 697.
71. (b) Drak, J.; Iwasawa, N.; Danishefsky, S. J.; Crothers, D. M. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 7464.
72. (c) Walker, S.; Landovitz, R.; Ding, W.-D.; Ellestad, G. A.; Kahne, D. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 4608.
73. (d) Aiyar, J.; Hitchcock, S. A.; Denhart, D.; Liu, K. K. C.; Danishefsky, S. J.; Crothers, D. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 855.
74. (e) Paloma, L. G.; Smith, J. A.; Chazin, W. J.; Nicolaou, K. C. J. Am. Chem. Soc. 1994, 116, 3697.
75. See also: (f) Kahne, D. Chem. Biol. 1995, 2, 7.
76. (a) Oppenheimer, N. J.; Chang, C.; Chang, L.-H.; Ehrenfeld, G.; Rodriguez, L. O.; Hecht, S. M. J. Biol. Chem. 1982, 257, 160 6.
77. (b) Hamamichi, N.; Natrajan, A.; Hecht, S. M. J. Am. Chem. Soc. 1992, 114, 6278.
78. (a) Sugiura, Y.; Suzuki, T.; Otsuka, M.; Kobayashi, S.; Ohno, M.; Takita, T.; Umezawa, H. J. Biol. Chem. 1983, 258, 1328.
79. (b) Umezawa, H.; Takita, T.; Sugiura, Y.; Otsuka, M.; Kobayashi, S.; Ohno, M. Tetrahedron 1984, 40, 501.
80. Denklan, D.; Köhnlein, W.; Lüders, G.; Stellmach, J. Z. Naturforsch. 1983, 38c, 939.