Aromatic layered guanidines bind sequence-specifically to DNA minor groove with precise fit

Tetrahedron Letters

Volumn 39, Issue 36, 1998, Pages 6475-6478

  Fukutomi, Ryuuta ^a   Tanatani, Aya ^a   Kakuta, Hiroki ^a   Tomioka, Nobuo ^b   Itai, Akiko ^b   Hashimoto, Yuichi ^a   Shudo, Koichi ^a   Kagechika, Hiroyuki ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b Inst of Medicinal Molecular Design   (Japan)

Author keywords

Guanidines; Molecular recognition; NMR; Nucleic acids

Indexed keywords

CONGOCIDINE; DOUBLE STRANDED DNA; GUANIDINE DERIVATIVE; NUCLEIC ACID; TETRAGUANIDINE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; CIRCULAR DICHROISM; COMPLEX FORMATION; CRYSTAL STRUCTURE; DNA BINDING; PROTON NUCLEAR MAGNETIC RESONANCE;

EID: 0032171670     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01378-1     Document Type: Article

References (17)

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10. (c) Tanatani, A.; Yamaguchi, K.; Azumaya, I.; Fukutomi, R.; Shudo, K.; Kagechika, H. J. Am. Chem. Soc. in press.
11. 8. Mizutani, M. Y.; Tomioka, N.; Itai, A. J. Mol. Biol. 1994, 243, 310-326.
12. 9. The crystal data of the duplex of 3 were obtained from the Protein Data Bank (1BNA)., Drew, H. R., Wing, R. M., Takano, T., Broka, C., Tanaka, S., Itakura, K. Dickerson, R. E. Proc. Natl. Acad. Sci. USA 1982, 75, 2179-83.
13. 10. Two enantiomeric structures of 1 and 2 were prepared by inverting the coordinates of the crystal structure, and at first the conformations were kept rigid during the docking. Several tens of stable possible docking models obtained by ADAM (ref. 8) runs were further optimized by the AMBER program package (ref. 11), allowing the movement of both the DNA duplex and 1 (or 2). The stable docking model shown in Figure 1b was selected based on the sum of the interaction energy between DNA and 1 and the intramolecular energy of 1.
14. 11. Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham III, T. E.; Ferguson, D. M.; Seibel, G. L.; Singh, U. C.; Weiner, P. K.; Kollman, P. A AMBER 4.1, 1992, University of California, San Francisco.
15. 12. Fukutomi, R.; Kagechika, H.; Hashimoto, Y.; Shudo, K. Chem. Pharm. Bull. 1996, 44, 1983-1985.
16. 13. Ultrafiltration assay was performed as follows: A mixture of a test compound and calf thymus DNA (0.1 mM) in TE buffer [10 mM Tris·HCl (pH 8) - 1 mM EDTA] was heated at 95 °C for 3 min, and allowed to stand at room temperature overnight. The mixture was ultrafiltered using a Microcon-10 UF tube (Amicon Co.) at 20 °C, then the concentration of the test compound in the filtrate was determined by HPLC (column Shiseido UG120Å). DNA-binding amount was calculated as the difference between the contents of the test compound in the filtrate in the presence and absence of DNA. The experiments using various concentrations of 1 or 2 afforded the binding constants (Ka) and number of binding sites per base pair (n) by Scatchard analysis.
17. 14. DNAs used in these experiments were confirmed to exist in B form by CD spectroscopy.