ORGANIC
LETTERS
2004
Vol. 6, No. 9
1349-1352
Synthesis and Peptide Binding
Properties of Methoxypyrrole Amino
Acids (MOPAS)
,†
Christoph Bonauer,† Manfred Zabel,‡ and Burkhard Ko1nig*
Institut fu¨r Organische Chemie and Zentrale Analytik, UniVersita¨t Regensburg,
D-93040 Regensburg, Germany
Received January 26, 2004
ABSTRACT
Methoxypyrrole amino acids (MOPAS) have been prepared and were introduced into small peptides with hairpin structures. The intra- and
intermolecular binding properties of this heterocyclic amino acid mimicking a dipeptido â-strand was investigated by NMR titration and X-ray
crystal structure analysis. The data reveal a hydrogen bonding pattern that is complementary to a peptide â-sheet.
The recognition of â-sheet structures is important for
protein-protein interactions1 as illustrated by many ex-
amples.2 Small organic molecules with a hydrogen bonding
pattern and structure complementary to â-sheets are promis-
ing for interception of protein-protein interaction, for
stopping protein aggregation,3 or stabilization4 or mimicking
â-sheet structures.5 The work on â-sheet recognition and
peptidomimetics6 has been extensively reviewed. Recently,
Chakraborty et al. introduced 5-(aminomethyl)pyrrole-2-
(4) Rzepecki, P.; Wehner, M.; Molt, O.; Zadmard, R.; Harms, K.;
Schrader, T. Synthesis 2003, 12, 1815-1826. Kirsten, C. N.; Schrader, T.
H. J. Am. Chem. Soc. 1997, 119, 12061-12068. Kemp, D. S.; Bowen, B.
R.; Muendel, C. C. J. Org. Chem. 1990, 55, 4650-4657. Kemp, D. S.
Trends Biotechnol. 1990, 8, 249-255. Kemp, D.; Bowen, B. R. Tetrahedron
Lett. 1988, 29, 5077-5080.
(5) Nowick, J. S.; Chung, D. M. Angew. Chem., Int. Ed. 2003, 42, 1765-
1768. Nowick, J. S.; Lam, K. S.; Khasanova, T. V.; Kemnitzer, W. E.;
Maitra, S.; Mee, H. T.; Liu, R. W. J. Am. Chem. Soc. 2002, 124, 4972-
4973. Nowick, J. S.; Smith, E. M.; Ziller, J. W.; Shaka, A. J. Tetrahedron
2002, 58, 727-739. Nowick, J. S.; Cary, J. M.; Tsai, J. H. J. Am. Chem.
Soc. 2001, 123, 5176-5180. Nowick, J. S.; Chung, D. M.; Maitra, K.;
Maitra, S.; Stigers, K. D.; Sun, Y. J. Am. Chem. Soc. 2001, 123, 1545-
1545. Junquera, E.; Nowick, J. S. J. Org. Chem. 1999, 64, 2527-2531.
Tsai, J. H.; Waldman, A. S.; Nowick, J. S. Bioorg. Med. Chem. 1999, 7,
29-38. Nowick, J. S.; Pairish, M.; Lee, I. Q.; Holmes, D. L.; Willer, J. W.
J. Am. Chem. Soc 1997, 119, 5413-5424. Nowick, J. S.; Holmes, D. L.;
Mackin, G.; Noronha, G.; Shaka, A. J.; Smith, E. M. J. Am. Chem. Soc.
1996, 118, 2764-2765. Nowick, J. S.; Mahrus, S.; Smith, E. M.; Ziller, J.
W. J. Am. Chem. Soc. 1996, 118, 1066-1072. Nowick, J. S.; Smith, E.
M.; Noronha, G. J. Org. Chem. 1995, 60, 7386-7387. Nowick, J. S.; Powell,
N. A.; Martinez, E. J.; Smith, E. M.; Noronha, G. J. Org. Chem. 1992, 57,
3763-3765.
† Institut fu¨r Organische Chemie.
‡ Zentrale Analytik.
(1) Maitra, S.; Nowick, J. S. In The Amide Linkage: Structural
Significance in Chemistry, Biochemistry, and Materials Science; Greenberg,
A., Breneman, C. M., Liebman, J. F., Eds.; John Wiley & Sons: New York
2000, Chapter 15.
(2) Binding of inhibitor to neuronal nitric oxide synthase: Liang, J.;
Jaffrey, Snyder, H. S.; Clardy, J. Nat. Struct. Biol. 1999, 6, 735-740.
Binding of Ras oncoproteins to Raf kinase: Nassar, N.; Horn, G.; Herrmann,
C.; Scherrer, A.; McCormick, F.; Wittinghofer, A. Nature 1995, 375, 554-
560. Homodimerization of HIV-1 protease: Zutshi, R.; Franciskovich, J.;
Shultz, M.; Schweitzer, B.; Bishop, P.; Wilson, M.; Chmielewski, J. J. Am.
Chem. Soc. 1997, 119, 4841-4845. Prion proteins: Prusiner, S. B. In Prions
Prions Prions; Springer: Berlin, 1996; Vol. 207. Mestel, R. Science 1996,
273, 184-189. Kuroda, Y.; Maeda, Y.; Nakagawa, T. J. Am. Chem. Soc.
2000, 122, 12596-12597.
(3) Nowick, J. S.; Chung, D. M.; Maitra, K.; Maitra, S.; Stigers, K. D.;
Sun, Y. J. Am. Chem. Soc. 2000, 122, 7654-7661. Boumendjel, A.; Roberts,
J. C.; Hu, E.; Pallai, P. V. J. Org. Chem. 1996, 61, 4434-4438. Michne,
W. F.; Schroeder, J. D. Int. J. Pept. Protein Res. 1996, 47, 2-8. Roberts,
J. C.; Pallai, P. V.; Rebek, J., Jr. Tetrahedron Lett. 1995, 36, 691-694.
(6) Glenn, M. P.; Fairlie, D. P. Mini ReV. Med. Chem. 2002, 2, 433-
445. Peczuh, M. W.; Hamilton, A. D. Chem. ReV. 2000, 100, 2479-2494.
Nowick, J. S. Acc. Chem. Res. 1999, 32, 287-296. Stigers, D. S.; Soth, M.
J.; Nowick, J. S. Curr. Opin. Chem. Biol. 1999, 3, 714-723. Nowick, J.
S.; Smith, E. M.; Pairish, M. Chem. Soc. ReV. 1996, 25, 401-415.
10.1021/ol049855x CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/27/2004