DOI QR코드

DOI QR Code

NMR Studies on Turn Mimetic Analogs Derived from Melanocyte-stimulating Hormones

  • Cho, Min-Kyu (Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University) ;
  • Kim, Sung-Soo (Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University) ;
  • Lee, Myung-Ryul (Department of Chemistry, College of Science, Yonsei University) ;
  • Shin, Joon (Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University) ;
  • Lee, Ji-Yong (Department of Chemistry, College of Science, Yonsei University) ;
  • Lim, Sung-Kil (Department of Internal Medicine, College of Medicine, Yonsei University) ;
  • Baik, Ja-Hyun (Clinical Research Center, College of Medicine, Yonsei University) ;
  • Yoon, Chang-Ju (Department of Chemistry, College of Science, Catholic University) ;
  • Shin, In-Jae (Department of Chemistry, College of Science, Yonsei University) ;
  • Lee, Weon-Tae (Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University)
  • Received : 2003.05.21
  • Accepted : 2003.06.04
  • Published : 2003.11.30

Abstract

Oligomers with $\alpha$-aminooxy acids are reported to form very stable turn and helix structures, and they are supposed to be useful peptidomimetics for drug design. A recent report suggested that homochiral oxa-peptides form a strong eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid residues in a $CDCl_3$ solution. In order to design an $\alpha$-MSH analog with a stable turn conformation, we synthesized four tetramers and one pentamer, based on $\alpha$-MSH sequence, and determined the solution structures of the molecules by two-dimensional NMR spectroscopy and simulated annealing calculations. The solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL) in DMSO-$d_6$ contain a stable 7-membered-ring structure that is similar to a $\gamma$-turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball-type rigid structure that is induced by strong hydrogen bonds between adjacent amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily prepared from natural or unnatural amino acids, can be employed to prepare peptidomimetic analogues with well-defined turn structures for pharmaceutical interest.

Keywords

References

  1. Armand, P., Kirshenbaum, K., Goldsmith, R. A., Farr-Jones, S.,Barron, A. E., Truong, K. T., Dill, K. A., Mierke, D. F.,Cohen, F. E., Zuckermann, R. N. and Bradley, E. K. (1998)NMR determination of the major solution conformation of apeptoid pentamer with chiral side-chains. Proc. Natl. Acad. Sci.USA 95, 4309-4314. https://doi.org/10.1073/pnas.95.8.4309
  2. Baek, B.-H., Lee, M.-R., Kim, K.-Y., Cho, U.-I., Boo, D. W. andShin, I. (2003) Novel consecutive beta- and gamma-turnmimetics composed of alpha-aminooxy tripeptides Org. Lett. 5,971-974. https://doi.org/10.1021/ol020233q
  3. Bax, A. and Davis, D. G. (1985) MLEV-17 based 2Dhomonuclear magnetization transfer spectroscopy. J. Magn.Reson. 65, 355-360.
  4. Bruger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros,P., Gross-Kunstleve, R. W., Jing, J.-S., Kuszewski, J., Nilges,M., Pannu, N. S., Read, R. J., Rice, L. M., Simonson, T. andWarren, G. (1998) Crystallography and NMR system-a newsoftware suite for macromolecular structure determination. ActaCryst. D54, 905-921.
  5. Chung Y. J., Huck, B. R., Christianson, L. A., Stanger, H. E.,Krauthauser, S., Powell, D. R. and Gellman, S. H. (2000)Stereochemical control of hairpin formation in beta-peptidescontaining dinipecotic acid reverse turn segments. J. Am. Chem.Soc. 122, 3995-4004. https://doi.org/10.1021/ja993416p
  6. Clore, G. M., Brunger, A. T., Karplus, M. and Gronenborn, A. M.(1986) Application of molecular dynamics with interprotondistance restraints to three-dimensional protein structuredetermination. A model study of crambin. J. Mol. Biol. 191,523-551. https://doi.org/10.1016/0022-2836(86)90146-4
  7. Crisma, M., Formaggio, F., Toniolo, C., Yoshikawa, T. andWakamiya, T. (1999) Flat peptides. J. Am. Chem. Soc. 121,3272-3278. https://doi.org/10.1021/ja9842114
  8. Datta, A. and Veeresa, G. (2000) A stereoselective route tohydroxyethylamine dipeptide isosteres. J. Org. Chem. 65, 7609-7611. https://doi.org/10.1021/jo001072b
  9. Davis, D. G. and Bax, A. (1985) Assignment of complex 1HNMR spectra via two-dimensional homonuclear Hartmann-Hahn spectroscopy. J. Am. Chem. Soc. 107, 2820-2821. https://doi.org/10.1021/ja00295a052
  10. Deziel, R., Plante, R., Caron, V., Grenier, L., Llinas-Brunet, M.,Duceppe, J.-S., Malenfant, E. and Moss, N. (1996) Practicaland diastereoselective synthesis of ketomethylene dipeptideisosteres of the type AA-psi(Coch2)Asp. J. Org. Chem. 61, 2901-2903. https://doi.org/10.1021/jo951988w
  11. Gante, J. (1994) Peptidomimetics-tailored enzyme inhibitors.Angew. Chem. Int. Ed. Engl. 33, 1699-1720. https://doi.org/10.1002/anie.199416991
  12. Gellman, S. H. (1998) Foldamers-A manifesto. Acc. Chem. Res.31, 173-180. https://doi.org/10.1021/ar960298r
  13. Hagihara, M., Anthony, N. J., Stout, T. J., Clardy, J. andSchreiber, S. L. (1992) Vinylogous polypeptides-an alternativepeptide backbone. J. Am. Chem. Soc. 114, 6568-6570. https://doi.org/10.1021/ja00042a052
  14. Huff, J. R. (1991) HIV Protease: A novel chemotherapeutic targetfor AIDS. J. Med. Chem. 34, 2305-2314. https://doi.org/10.1021/jm00112a001
  15. Huixiong, C., Noble, F., Coric, P., Fournie-Zaluski, M. andRoques, B. P. (1998) Aminophosphinic Inhibitors as Transition-stateanalogs of enkephalin-degrading enzymes-a class ofcentral analgesics. Proc. Natl. Acad. Sci. USA 96, 12028-12033.
  16. Kirshenbaum, K., Barron, A. E., Goldsmith, R. A., Armand, P.,Bradley, E. K., Truong, K. T., Dill, K. A., Cohen, F. E. andZuckermann, R. N. (1998) Sequence-Specific Polypeptoids - ADiverse Family of Heteropolymers with Stable SecondaryStructure. Proc. Natl. Acad. Sci. USA 95, 4303-4308. https://doi.org/10.1073/pnas.95.8.4303
  17. Koo, B. -K., Kim, M. -H., Lee, S. -T. and Lee, W. (2002)Purification and spectroscopic characterization of the humantyrosine kinase-6 SH3 domain. J. Biochem. Mol. Biol. 35, 343-347. https://doi.org/10.5483/BMBRep.2002.35.3.343
  18. Li, S.-Z., Lee, J.-H., Lee, W., Yoon, C.-J., Baik, J.-H. and Lim, S.-K. (1999) Type I ${\beta}-turn$ conformation is important forbiological activity of the melanocyte-stimulating hormoneanalogues. Eur. J. Biochem. 265, 1-12. https://doi.org/10.1046/j.1432-1327.1999.00765.x
  19. Peter, C., Daura, X. and van Gunsteren, W. F. (2000) Peptides ofaminoxy acids: A molecular dynamics simulation study ofconformational equilibria under various conditions. J. Am.Chem. Soc. 122, 7461-7466. https://doi.org/10.1021/ja000873t
  20. Shin, I., Lee, M-r., Lee, J., Jung, M., Lee, W. and Yoon, J. (2000)Synthesis of optically-active phthaloyl D-aminooxy acids fromL-amino-acids or L-hydroxy acids as building-blocks for thepreparation of aminooxy peptides. J. Org. Chem. 65, 7667-7675. https://doi.org/10.1021/jo0006573
  21. Sieburth, S. M., Nittoli, T., Mutahi, A. M. and Guo, L. (1998)Silanediols-A new class of potent protease inhibitor. Angew.Chem. Int. Ed. 37, 812-814. https://doi.org/10.1002/(SICI)1521-3773(19980403)37:6<812::AID-ANIE812>3.0.CO;2-I
  22. Smith, A. B. III., Benowitz, A. B., Sprengeler, P. A., Barbosa, J.,Guzman, M. C., Hirshmann, R., Schweiger, E. J., Bolin, D. R.,Nagy, Z., Campbell, R. M., Cox, D. C. and Olson, G. L.(1999) Design and synthesis of a competent pyrrolinonepeptidehybrid ligand for the class-II major histocompatibilitycomplex protein HLA-DR1. J. Am. Chem. Soc. 121, 9286-9298. https://doi.org/10.1021/ja991251e
  23. Yang, D., Ng, F.-F., Li, Z.-J., Wu, Y.-D., Chan, K. W. K. andWang, D. -P. (1996) An unusual turn structure in peptidescontaining alpha-aminoxy acids. J. Am. Chem. Soc. 118, 9794-9795. https://doi.org/10.1021/ja960515j
  24. Yang, D., Qu, J., Ng, F.-F., Wang, X.-C., Cheung, K.-K., Wang,D.-P. and Wu, Y.-D. (1999) Novel turns and helices in peptidesof chiral alpha-aminoxy acids. J. Am Chem. Soc. 121, 589-590. https://doi.org/10.1021/ja982528y
  25. Wu, Y.-D., Wang, D.-P., Chan, K. W. K. and Yang, D. (1999)Theoretical-study of peptides formed by aminoxy acids. J. Am.Chem. Soc. 121, 11189-11196. https://doi.org/10.1021/ja9918019
  26. Wuthrich, K. (1986) NMR of proteins and nucleic acids, Wiley,New York, USA.

Cited by

  1. Structure?function Relationships and Conformational Properties of ?-MSH(6?13) Analogues with Candidacidal Activity vol.69, pp.1, 2007, https://doi.org/10.1111/j.1747-0285.2007.00473.x
  2. Fixierung cyclischer Peptide: Mimetika von Proteinstrukturmotiven vol.126, pp.48, 2014, https://doi.org/10.1002/ange.201401058
  3. Constraining Cyclic Peptides To Mimic Protein Structure Motifs vol.53, pp.48, 2014, https://doi.org/10.1002/anie.201401058