2'-Deoxyribo-PNAs: A structurally novel class of polyamide nucleic acids with good RNA and DNA binding affinity

Tetrahedron Letters

Volumn 40, Issue 15, 1999, Pages 2899-2902

  Von Matt, Peter ^a   De Mesmaeker, Alain ^a   Pieles, Uwe ^b   Zürcher, Werner ^a   Altmann, Karl Heinz ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b ALTANA PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEIC ACID; POLYAMIDE;

ARTICLE; BINDING AFFINITY; CHIMERA; DNA BINDING; DNA DNA HYBRIDIZATION; DRUG STABILITY; DRUG SYNTHESIS; HYDROLYSIS; STRUCTURE ANALYSIS;

EID: 0033537904     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00389-5     Document Type: Article

References (32)

1. (a) De Mesmaeker, A; Häner, R.; Martin, P.; Moser, H. E. Acc. Chem. Res. 1995, 28, 366-374.
2. (b) De Mesmaeker, A.; Altmann, K.-H.; Waldner, A.; Wendeborn, S. Curr. Opinion Struct. Biol. 1995, 5, 343-355.
3. (c) Varma, R. S. Synlett 1993, 621-637.
4. (a) Crooke, S. T. Med. Res. Rev. 1996, 16, 319-344.
5. (b) Altmann, K.-H.; Dean, N. M.; Fabbro, D.; Freier, S. M.; Geiger, T.; Häner, R.; Hüsken, D.; Martin, P.; Monia, B. P.; Müller, M.; Natt, F.; Nicklin, P.; Phillips, J.; Pieles, U.; Sasmor, H.; Moser, H. E. Chimia 1996, 50, 168-176.
6. (c) Milligan, J. F.; Matteucci, M. D.; Martin, J. C. J. Med. Chem. 1993, 36, 1923-1937.
7. (d) Uhlmann, E.; Peyman, A. Chem. Rev. 1990, 90, 543-584.
8. (a) De Mesmaeker, A.; Lesueur, C.; Bévièrre, M.-O.; Waldner, A.; Fritsch, V.; Wolf, R. M. Angew. Chemie Int. Ed. Engl. 1996, 35, 2790-2794.
9. (b) De Mesmaeker, A.; Waldner, A.; Lebreton, J.; Hoffmann, P.; Fritsch, V.; Wolf, R. M.; Freier, S. M. Angew. Chem. Int. Ed. Engl. 1994, 33, 226-229.
10. (c) Lebreton, J.; Waldner, A.; Lesueur, C.; De Mesmaeker, A. Synlett 1994, 137-140.
11. (d) Idziak, I.; Just, G.; Damha, M. J.; Giannaris, P. A. Tetrahedron Lett. 1993, 34, 5417-5420.
12. (a) Ref 1c.
13. (b) Hyrup, B.; Nielsen, P. E. Bioorg. Med. Chem. 1996, 4, 5-23.
14. (c) Noble, S. A.; Bonham, M. A.; Bisi, J. E.; Bruckenstein, D. A.; Brown, P. H.; Brown, S. H.; Cadilla, R.; Gaul, M. D.; Hanvey, J. C.; Hassman, C. F.; Josey, J. A.; Luzzio, M. J.; Myers, P. M.; Pipe, A. J.; Ricca, D. J.; Su, C. W.; Stevenson, C. L.; Thomson, S. A.; Wiethe, R. W.; Babiss, L. E. Drug Dev. Res. 1995, 34, 184-195.
15. (d) Goodnow, R. A. Jr.; Richou, A.-R.; Tam, S. Tetrahedron Lett. 1997, 38, 3195-3198.
16. (e) Goodnow, R. A. Jr.; Tam, S.; Pruess, D. L.; McComas, W. W. Tetrahedron Lett. 1997, 38, 3199-3202.
17. Such hybrid structures could be of particular interest in the design of antisense molecules capable of eliciting RNAse H-mediated cleavage of bound target mRNA. (a) Monia, B. P.; Lesnik, E. A.; Gonzalez, C.; Lima, W. F.; McGee, D.; Guinosso, C. J.; Kawasaki, A. M.; Cook, P. D.; Freier, S. M. J. Biol. Chem. 1993, 268, 14514-14522.
18. (b) Giles, R. V.; Tidd, D. M. Nucleic Acids Res. 1992, 20, 763-770.
19. Lin, T.-S.; Prusoff, W. H. J. Med. Chem. 1978, 21, 109-112.
20. Green, M.; Berman, J. Tetrahedron Lett. 1990, 31, 5851-5852.
21. Samano, V.; Robins, M. J. Synthesis 1991, 283-288. Divakar, K. J.; Reese, C. B. J. Chem. Soc. Perkin I 1982, 1171-1176.
22. Samano, V.; Robins, M. J. Synthesis 1991, 283-288. Divakar, K. J.; Reese, C. B. J. Chem. Soc. Perkin I 1982, 1171-1176.
23. McBride, L. J.; Kierzek, R.; Beaucage, S. L.; Caruthers, M. H. J. Am. Chem. Soc. 1986, 108, 2040-2048.
24. Just et. al. have independently synthesized a N(4)-benzoyl protected cytidine derivative corresponding to However, they did not report further elaboration of this compound. See: Grunder-Klotz, E.; Just, G. Nucleosides & Nucleotides 1994, 13, 1829-1841.
25. Gait, M. J. Oligonucleotide Synthesis: A Practical Approach, IRL, Oxford, 1984.
26. Atherton, E.; Sheppard, R. C. J. Chem. Soc., Chem. Commun. 1985, 165-166.
27. Activated ester 20 was also employed for the incorporation of the 5′-terminal thymidine unit in analog I, while a building block related to 22 was used for the 3′-terminal thymidine unit in III. For 22; see: Bannwarth, W. Helv. Chim. Acta 1988, 71, 1517-1527. (equation presented) For an automated solid-phase synthesis of PNA-(5′)-DNA-(3′)-PNA chimera, see also: Van der Laan, A. C.; Brill, R.;Kiumelis, R. G.; Kuyl-Yeheskiely, E.; Van Boom, J. H.; Andrus, A.; Vinayak, R. Tetrahedron Lett. 1997, 38, 2249-2252.
28. Activated ester 20 was also employed for the incorporation of the 5′-terminal thymidine unit in analog I, while a buildingblock related to 22 was used for the 3′-terminal thymidine unit in III. For 22; see: Bannwarth, W. Helv. Chim. Acta 1988, 71,1517-1527. (equation presented) For an automated solid-phase synthesis of PNA-(5′)-DNA-(3′)-PNA chimera, see also: Van der Laan, A. C.; Brill, R.; Kiumelis, R. G.; Kuyl-Yeheskiely, E.; Van Boom, J. H.; Andrus, A.; Vinayak, R. Tetrahedron Lett. 1997, 38, 2249-2252.
29. Phosphorylations were achieved according to previously published procedures and involved use of a β-eliminative support for the solid-phase synthesis of I (introduction of the 3′-phosphate group; Efimov, V. A.; Buryakova, A. A.; Reverdatto, S. V.; Chakhmakhcheva, O. G.; Ovchinnikov, Y. A. Nucl. Acids Res. 1983, 11, 8369-8387) as well as reaction of the 5′-hydroxyl group of the support-bound oligonucleotide analog with bis(β-cyanoethoxy)-N,N-diisopropylphosphite and subsequent oxidation with tert-butyl hydroperoxide (Horn, T; Urdea, M. S. DNA 1986, 5, 421-426).
30. Phosphorylations were achieved according to previously published procedures and involved use of a β-eliminative supportfor the solid-phase synthesis of I (introduction of the 3′-phosphate group; Efimov, V. A.; Buryakova, A. A.; Reverdatto, S.V.; Chakhmakhcheva, O. G.; Ovchinnikov, Y. A. Nucl. Acids Res. 1983, 11, 8369-8387) as well as reaction of the 5′-hydroxyl group of the support-bound oligonucleotide analog with bis(β-cyanoethoxy)-N,N-diisopropylphosphite andsubsequent oxidation with tert-butyl hydroperoxide (Horn, T; Urdea, M. S. DNA 1986, 5, 421-426).
31. After purification by polyacrylamide gel electrophoresis, oligonucleotide analogs I - V were obtained in >95% purity in all five cases as determined by capillary gel electrophoresis. Analysis of the purified products by MALDI-TOF mass spectrometry confirmed the expected molecular weights (Pieles, U.; Zürcher, W.; Schär, M.; Moser, H. Nucleic Acids Res. 1993, 21, 3191-3196). I: calc. mass: 4109, found: 4112. II: calc.: 4243, found: 4244. III: calc.: 4272, found: 4281. IV: calc.: 4232, found: 4231.
32. The lack of hysteresis is indicative of the absence of triple helix formation, as the isosequential PNA showed a large hysteresis in thermal melting experiments. K.-H. Altmann, D Hüsken, unpublished results.