Enhanced DNA photocleavage and binding properties of sapphyrin-polyamine conjugates

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 11, 1997, Pages 1433-1436

  Sessler, Jonathan L ^a   Andrievsky, Andrei ^a   Sansom, Petra I ^a   Král, Vladimír ^a   Iverson, Brent L ^a  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHOTOSENSITIZING AGENT; PORPHYRIN DERIVATIVE; SAPPHYRIN DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DNA BINDING; DNA CLEAVAGE; DRUG SYNTHESIS; MODULATION; PHOTODEGRADATION;

EID: 0030910961     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00237-0     Document Type: Article

References (17)

1. (a) Kochevar, I. E.; Dunn, D. A. In Bioorganic Photochemistry: Photochemistry and Nucleic Acids; Morrison, H., Ed.; Wiley: New York, 1989; Vol 1, pp 273-315.
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3. (a) Sessler, J. L.; Sansom, P. L; Král, V.; O'Connor, D.; Iverson, B. L. J. Am. Chem. Soc. 1996, 118, 12322.
4. (b) Magda, D.; Wright, M.; Miller, R. A.; Sessler, J. L.; Sansom, P. I. J. Am. Chem. Soc. 1995, 117, 3629.
5. Wan, S.; Parrish, J. A.; Anderson, R. R.; Madden, M. Photochem. Photobiol. 1981, 34, 679.
6. The synthesis of sapphyrin 1 has been described previously: Král, V.; Furuta, H.; Shreder, K.; Lynch, V.; Sessler, J. L. J. Am. Chem. Soc. 1996, 118, 1595.
7. Iverson, B. L.; Shreder, K.; Král, V.; Sansom, P.; Lynch, V.; Sessler, J. L. J. Am. Chem. Soc. 1996, 118, 1608.
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10. The synthesis of sapphyrin 5 has been described previously: Král, V.; Sessler, J. L.; Furuta, H. J. Am. Chem. Soc. 1992, 114, 8704.
11. The general synthetic procedure is as follows: Sapphyrin bisacid 5(1 equiv) was dissolved under argon in anhydrous DMF. 1.1′-Carbonyldiimidazole (CDI) (3 equiv) was added, followed by a catalytic amount of 1-hydroxybenzotriazole hydrate (HOBt). The resulting mixture was stirred at room temperature under argon for 2 h. A solution of t-Boc-protocted amine (3 equiv) in DMF was added, and the resulting mixture was stirred at room temperature under argon for 24 h. The solvent was evaporated off, and the protected amine was purified via column chromatography on silica gel using ammonia-saturated methanol/dichloromethane (2-20% v/v gradient) as the eluent. The solvent was evaporated and the compound was deprotected using HC1-saturated chloroform/methanol (3:1) for ca. 2-7 h (TLC control). The solvents were evaporated, and the product was dried in vacou. Satisfactory spectroscopic and analytical data were obtained for all new compounds.
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14. Photocleavage was monitored using wavelengths above 300 nm since the cleavage efficiency is maximal in this range.
15. The high level of inhibition for sapphyrin 1 may be rationalized by its relatively low DNA binding affinity and photocleavage as compared with those of sapphyrins 2-4.
16. (a) Cain, B. F.; Bagutey, B. C.; Denny, W. A. J. Med. Chem. 1978, 21, 658.
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