Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Efficient Macrocyclization for Cyclicpeptide Using Solid-Phase Reaction

  • Kim, Joong-Hup (Korea Institute of Science and Technology) ;
  • Hong, Il-Khee (Department of Pharmaceutical Science. College of Pharmacy, Kyung Hee University) ;
  • Kim, Hyo-Jeong (Department of Pharmaceutical Science. College of Pharmacy, Kyung Hee University) ;
  • Jeong, Hyeh-Jean (Department of Pharmaceutical Science. College of Pharmacy, Kyung Hee University) ;
  • Choi, Moon-Jeong (Korea Institute of Science and Technology) ;
  • Yoon, Chang-No (Korea Institute of Science and Technology) ;
  • Jeong, Jin-Hyun (Department of Pharmaceutical Science. College of Pharmacy, Kyung Hee University)
  • Published : 2002.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

Cyclicpeptides are important targets in peptide synthesis because of their interesting biological properties. Constraining highly flexible linear peptides by cyclization is one of the mostly widely used approaches to define the bioactive conformation of peptides. Cyclic peptides often have increased receptor affinity and metabolic stability over their linear counterparts. We carried out virtual screening experiment via docking in order to understand the interaction between HLE-Human Leukocyte Elastase and ligand peptide and to identify the sequence that can be a target in various ligand peptides. We made cyclic peptides as a target base on Metlle-Phe sequence having affinity for ligand and receptor active site docking. There are three ways to cyclize certain sequences of amino acids such as Met-lie-Phe-Gly-Ile. First is head-to-tail cyclization method, linking between N-terminal and C-terminal. Second method utilizes amino acid side chain such as thiol functional group in Cys, making a thioether bond. The last one includes an application of resin-substituted amino acids in solid phase reaction. Among the three methods, solid phase reaction showed the greatest yield. Macrocyclization of Fmoc-Met-Ile-Phe-Gly-Ile-OBn after cleavage of Fmoc protection in solution phase was carried out to give macrocyclic compound 5 in about 7% yield. In the contrast with solution phase reaction, solid phase reaction for macrocyclization of Met-Ile-Phe-Gly-Ile-Asp-Tentagel in normal concentrated condition gave macrocyclic compound 7 in more than 35% yield.

Keywords

References

  1. Brown, H. C., Kramer, G. W., Levy, A. B., Midland, M. M., Organic Synthesis via Boranes, John-Wiley: New York, Chapter 9. (1975)
  2. Coxon, J. M., Dansted, E., Hartshorn, M. A, Allylic Oxidation with hydrgenperoxide/Selenium dioxide: trans-pinocarveol. Org. Synth. Coli., 6, 946-951 (1988)
  3. Dolle, R. E., Nelson, Jr, K. H., Comprehensive Survey of Combinatorial Library Synthesis. J. Combi. Chem., 235-282 (1999)
  4. Fujii, K., Ikai, Y Oka, H., Suzuki, M. A, Nonempirical Method Using LC/MS for Determination of the Absolute Cor figuration of Constituent Amino Acids in a Peptide: Combnation of Marfey's Method with Mass Spectrometry and Its Practical Application. Anal. Chem., 69, 5146-5151 (1997) https://doi.org/10.1021/ac970289b
  5. Gordon, E. M., Gallop, M. A., Patal, D. V.. Strategy and Tactics in Combinatorial Organic Synthesis. Applications to Drug Discovery. Ace. Chem. Res., 29, 144-154 (1996)
  6. Graf von Roedern, E., Lohof, E., Hessler, G. Synthesis and Conformational Analysis of Linear and Cyclic Peptides Containing Sugar Amino Acids. J. Am. Chem. Soc., 118, 10156-10167 (1996) https://doi.org/10.1021/ja961068a
  7. Herzig, J., Nudelman, A; Gottlieb, H.E.; Fischer, B. Studies in Sugar Chemistry.2.A simple method for O-Deacylation of polyacylated sugars. J. Org. Chem., 51, 727-730 (1986) https://doi.org/10.1021/jo00355a026
  8. Holmes, D. L., Smith, E.M.; Nowick, J.S. Solid-Phase Synthesis of Artificial-Sheets. J. Am. Chem. Soc., 119, 7665-7669 (1997) https://doi.org/10.1021/ja9710971
  9. Jain, T. C., Banks, C. M., Mccloskey, J. E., Dehydrosaussurea lactonefrom costunolideand reversibility in the germacranolidecope reaction. Tetrahedron Lett., 11, 841-844 (1970) https://doi.org/10.1016/S0040-4039(01)97846-3
  10. Kistaludy, L., Mohacsi, T, Low, M., Drexler, F. Pentafluorophenyl acetate: a new, highly selective acetylating agent. J. Org. Chem., 44, 654-656 (1979) https://doi.org/10.1021/jo01318a047
  11. Kobayashi, S., New methodologies for the synthesis of compound libraries. Chem. Soc. Rev., 28, 1-16 (1999) https://doi.org/10.1039/a707429h
  12. Mavromoustakos, T., Kolocouris, A., Zervou, M., An Effort To Understand the Molecular Basis of Hypertension through the Study of Conformational Analysis of Losartan and Sarmesin Using a Combination of Nuclear Magnetic Resonance Spectroscopy and Theoretical Calculations. J. Med. Chem., 42, 1714-1722 (1999) https://doi.org/10.1021/jm980499w
  13. Njoroge, F. G., Vibulbhan, B., Rane, D. F., Bishop, W.R., Petrin, J., Patton, R., Bryant, M. S., Chen, K .-J., Nomeir, A. A., Lin, C.-C., Liu, M., King, I., Chen, J., Lee, S., Yaremko, B., Dell, J., Lipari, P., Malkowski, M., Li, Z., Catino, J., Doll, R .J., Girijavallabhan, V., Ganguly,A.K., Structure-Activity Relationship of 3-Substituted N-(Pyridinylacetyl)-4-(8-chloro-5,6-dihydro-11H-benzo [5,6]cyclohepta[1,2-b]pyridin-11-vlidene)-piperidine Inhibitors of Farnesyl-Protein Transferase: Design and Synthesis of in Vivo Active Antitumor Compounds. J. Med. Chem., 40, 4290-4301 (1997).￿羙䥇萀﷿￿ﾙ䥇蘀ｿᮚ䥇蜀܀肚䥇言￿鞚䥇謀￿ﾚ䥇踀￿羛䥇鈀Ѐ鲛䥇錀܀œ䥇阀￿羜䥇騀￿￿䥇鴀￿７䩇ꀀ耘䩇ꌀ਀䩇ꘀ刺￿缙䩇꜀̀䩇꤀ఀ耚䩇꬀﫿￿：䩇관Ѐ耛䩇뀀ఀ䩇대ﯿ￿缜䩇됀฀€鰜䩇딀Ȁ€䩇렀ﳿ￿ﾗ䩇먀؀肘䩇묀￿ﾘ䩇밀﷿￿羙䩇븀܀š䩇뼀￿羚䩇섀￿￿ﾚ䩇쌀ऀ肛䩇쐀￿ﾛ䩇였￿￿羜䩇윀ࠀ䭇쬀Ā䭇찀଀耘䭇촀￿８䭇츀Ȁ耙䭇 https://doi.org/10.1021/jm970464g
  14. Oian, L., Sun, Z., Deffo, T., Mertes, K. B. A., Convenient synthesis of macrocyclic lactams. Tetrahedron Lett., 31, 6469-6472 (1990) https://doi.org/10.1016/S0040-4039(00)97093-X
  15. Reichwein, J. F., Versluis, C., Liskamp, R. M. J., Synthesis of Cyclic Peptides by Ring-Closing Metathesis. J. Org. Chem., 65, 6187-6195 (2000) https://doi.org/10.1021/jo000759t
  16. Schmidt, R., Neubert, K., Int. J. Peptide Protein. Res., 37, 502-(1991) https://doi.org/10.1111/j.1399-3011.1991.tb00767.x
  17. Shioiri, T., Ninomiya, K., Yamada, S., Diphenylphosphoryl azide. New convenient reagent for a modified Curtius reaction and for peptide synthesis. J. Am. Chem. Soc., 94, 6203-6205 (1972) https://doi.org/10.1021/ja00772a052
  18. Spatola, A. F., Crozet, Y., Dewit, D. Rediscovering an Endothelin Antagonist (BO-123): A Self-Deconvoluting Cyclic Pentapeptide Library. J. Med. Chem., 39, 3842-3846 (1996) https://doi.org/10.1021/jm9604078
  19. Still, W. C., Kahn, M., Mitra, A., Homo-C-nucleosides. Synthesis of certain 6-substituted 4-pyrimidinones. J. Org. Chem., 43, 2923-2925 (1978) https://doi.org/10.1021/jo00408a041