Bifunctional rhodium intercalator conjugates as mismatch-directing DNA alkylating agents

Journal of the American Chemical Society

Volumn 126, Issue 28, 2004, Pages 8630-8631

  Schatzschneider, Ulrich ^a   Barton, Jacqueline K ^a  

^a California Institute of Technology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYLATING AGENT; ANILINE MUSTARD; DNA; MELPHALAN; RHODIUM;

ARTICLE; DNA ALKYLATION; DNA CLEAVAGE; DNA DENATURATION; DNA STRUCTURE; DRUG DESIGN; MISMATCH REPAIR; PHOTOACTIVATION; REACTION ANALYSIS; THERMODYNAMICS;

2,2'-DIPYRIDYL; ALKYLATING AGENTS; ALKYLATION; BASE PAIR MISMATCH; BINDING SITES; CHRYSENES; DNA; INTERCALATING AGENTS; LIGANDS; MACROMOLECULAR SUBSTANCES; MOLECULAR STRUCTURE; ORGANOMETALLIC COMPOUNDS; PHENANTHROLINES; RHODIUM; SUBSTRATE SPECIFICITY;

EID: 3242684962     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja048543m     Document Type: Article

References (26)

1. Wood, R. D. Annu. Rev. Biochem. 1996, 65, 135-167.
2. Hoeijmakers, J. H. J. Nature 2001, 411, 366-374.
3. Schärer, O. D. Angew. Chem., Int. Ed. 2003, 42, 2946-2974.
4. Bürmeyer, A. B.; Deschenes, S. M.; Baker, S. M.; Liskay, R. M. Annu. Rev. Genet. 1999, 33, 533-564.
5. Jiricny, J.; Nyström-Lahti, M. Curr. Opin. Genet. Dev. 2000, 10, 157-161.
6. Jackson, B. A.; Barton, J. K. J. Am. Chem. Soc. 1997, 119, 12986-12987.
7. Jackson, B. A.; Alekseyev, V. Y.; Barton, J. K. Biochemistry 1999, 38, 4655-4662.
8. Jackson, B. A.; Barton, J. K. Biochemistry 2000, 39, 6176-6182.
9. Junicke, H.; Hart, J. R.; Kisko, J. L.; Glebov, O.; Kirsch, I. R.; Barton, J. K. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 3737-3742.
10. Rüba, E.; Hart, J. R.; Barton, J. K. Inorg. Chem., published online May 26, 2004 http://dx.doi.org/10.1021/ic0499291.
11. Kielkopf, C. L.; Erkkila, K. E.; Hudson, B. P.; Barton, J. K.; Rees, D. C. Nat. Struct. Biol. 2000, 7, 117-121.
12. Kohn, K. W.; Hartley, J. A.; Mattes, W. B. Nucleic Acid Res. 1987, 15, 10531-10549.
13. Hartley, J. A.; Gibson, N. W.; Kohn, K. W.; Mattes, W. B. Cancer Res. 1986, 46, 1943-1947.
14. Mattes, W. B.; Hartley, J. A.; Kohn, K. W. Nucleic Acid Res. 1986, 14, 2971-2987.
15. Denny, W. A. Curr. Med. Chem. 2001, 8, 533-544.
16. (a) Gourdie, T. A.; Valu, K. K.; Gravatt, G. L.; Boritzki, T. J.; Baguley, B. C.; Wakelin, L. P. G.; Wilson, W. R.; Woodgate, P. D.; Denny, W. A. J. Med. Chem. 1990, 33, 1177-1186.
17. (b) Gravatt, G. L.; Baguley, B. C.; Wilson, W. R.; Denny, W. A. J. Med. Chem. 1991, 34, 1552-1560.
18. (c) Gravatt, G. L.; Baguley, B. C.; Wilson, W. R.; Denny, W. A. J. Med. Chem. 1994, 37, 4338-4345.
19. Boger D. L.; Garbaccio, R. M. Acc. Chem. Res. 1999, 32, 1043-1052.
20. Wurtz, N. R.; Dervan, P. B. Chem. Biol. 2000, 7, 153-161.
21. Wang, Y.-D.; Dziegielewski, J.; Wurtz, N. R.; Dziegielewska, B.; Dervan, P. B.; Beerman, T. A. Nucleic Acid Res. 2003, 31, 1208-1215.
22. McClean, S.; Costelloe, C.; Denny, W. A.; Searcey, M.; Wakelin, L. P. G. Anti-Cancer Drug Des. 1999, 14, 187-204.
23. Mürner, H.; Jackson, B. A.; Barton, J. K. Inorg. Chem. 1998, 37, 3007-3012.
24. Sitlani, A.; Long, E. C.; Pyle, A. M.; Barton, J. K. J. Am. Chem. Soc. 1992, 114, 2303-2312.
25. Given the lack of complete reaction with piperidine, the relative intensities at the two sites may not reflect the relative amounts of alkylation.
26. The amount of cleavage due to alkylation at the 5′-G of the distal 5′-GNC-3′ site is 1.0%, and at the 5′-G of the proximal site it is 0.4% (lane 4). The damage due to direct photocleavage alone is 0.3% (lane 5). The sum of these two values is similar to the combined effects of alkylation and photocleavage, 0.7% in lane 6. Also, the amount of photocleavage at the 5′-G of the proximal site in the presence of conjugate 1 is similar to that observed with untethered intercalator 2 (0.3% in lane 7).