Synthesis of DNA-binding heteroaromatic oligoamides on liquid solid support

(Note: The full text of this document is currently only available in the PDF Version )

Burkhard König


Abstract

Heteroaromatic oligoamides as building blocks for the synthesis of sequence specific DNA binding molecules are obtained from nitro carboxylic acids on polyethylene glycol without the use of protecting groups


References

  1. There are five main peptide structural motifs for DNA-binding that have been identified: helix-turn-helix, zinc finger, leucine zipper, helix-loop-helix and antiparallel β-sheets (β-ribbon). D. S. Johnson and D. L. Boger, in Comprehensive Supramolecular Chemistry, ed. J. L. Atwood, J. E. Davies, D. D. Macnicol, F. Vögtle and J.-M. Lehn, Elsevier Science, Oxford, 1996, vol. 4, p. 77 Search PubMed .
  2. For a recent example of the regulation of genes expression by small molecules, see: J. M. Gottesfeld, L. Neely, J. W. Trauger, E. E. Baird and P. B. Dervan, Nature, 1997, 387, 202 Search PubMed .
  3. (a) P. E. Nielsen, Chem. Eur. J., 1997, 3, 505 CrossRef CAS  and references cited therein; (b) The structure of the heteroaromatic peptides was inspired by DNA-binding natural products, such as distamycin or netropsin: D. S. Johnson and D. L. Boger, in Comprehensive Supramolecular Chemistry, ed. J. L. Atwood, J. E. Davies, D. D. Macnicol, F. Vögtle and J.-M. Lehn, Elsevier Science, Oxford, 1996, vol. 4, p. 73 Search PubMed ; (c) New J. Chem., 1997, 21, 1(special issue) Search PubMed .
  4. E. E. Baird and P. B. Dervan, J. Am. Chem. Soc., 1996, 118, 6141 CrossRef CAS .
  5. Heteroaromatic oligopeptides with terminal pyridine, thiazole and furan units have been synthesized. These derivatives were expected to bind preferentially G-C rich regions. However, in most cases they still show a preference for A-T regions; K. E. Rao, R. G. Shea, B. Yadagiri and J. W. Lown, Anti-Cancer Drug Des., 1990, 5, 3 Search PubMed  (terminal thiazol) M. Lee, R. G. Shea, J. W. Lown and R. T. Pon, J. Mol. Recogn., 1989, 2, 6 Search PubMed  (furan)a terminal pyridine has been found to be G-C specific in certain cases: W. S. Wade, M. Mrksich and P. B. Dervan, J. Am. Chem. Soc., 1992, 114, 8783 Search PubMed .
  6. For the use of poly(ethylene glycol) as support in synthesis, see: M. Mutter, H. Hagenmaier and E. Bayer, Angew. Chem., 1971, 83, 883 Search PubMed ; Angew. Chem., Int. Ed. Engl., 1971, 10, 811 ; R. N. V. Pillai and M. Mutter, Top. Curr. Chem., 1982, 106, 119 ; D. J. Gravert and K. D. Janda, Chem. Rev., 1997, 97, 489 Search PubMed  combinatorial libraries: H. Han, M. M. Wolfe, S. Brenner and K. D. Janda, Proc. Natl. Acad. Sci. USA, 1995, 92, 6419 .
  7. The coupling with DCC–DMAP gave 6 in a lower yield of 92% .
  8. M. A. Tilak and C. S. Hollinden, Tetrahedron Lett., 1968, 1297 CrossRef CAS .
  9. M. Mrksich, M. E. Parks and P. B. Dervan, J. Am. Chem. Soc., 1994, 116, 7983 CrossRef CAS  MeO-PEG support is not suitable for a direct synthesis of extended structures due to the known alteration of its physical properties with growing oligoamide chain length. This leads to incomplete precipitation.
  10. B. König, H. Buchholz, M. Rödel and M. Schulze, patent pending .
  11. Recent example: S. M. Touami, C. C. Poon and P. A. Wender, J. Am. Chem. Soc., 1997, 119, 7611 Search PubMed .
  12. Many carbo- or hetero-cyclic aromatic nitro carboxylic acids are readily available; 4-nitrothiophene-2-carboxylic acid: M. Römer, Chem. Ber., 1887, 20, 116 Search PubMed  ethyl-1-methyl-4-nitroimidazole- 2-carboxylate: K. Krowicki and J. W. Lown, J. Org. Chem., 1987, 52, 3493 Search PubMed  5-nitrothiophene-2-carboxylic acid: P. Cogolli, F. Maiolo, L. Testaferri, M. Tiecco and M. Tingoli, J. Chem. Soc., Perkin Trans. 2, 1980, 1331 Search PubMed  2-nitrothiazole-5-carboxylic acid: W. Knauf, Eur. J. Med. Chem. Chim. Ther., 1975, 10, 533 CrossRef CAS .
Click here to see how this site uses Cookies. View our privacy policy here.