Efficient macrocyclization for cyclicpeptide using solid-phase reaction

Joonghup Kim, Il Khee Hong, Hyo Jeong Kim, Hyeh Jean Jeong, Moon Jeong Choi, Chang No Yoon, Jin Hyun Jeong

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 Met-Ile-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-Ile-Phe-Gly-Ile. First is head-totail 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.

Original languageEnglish
Pages (from-to)801-806
Number of pages6
JournalArchives of pharmacal research
Volume25
Issue number6
DOIs
Publication statusPublished - 2002 Dec 31

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Kim, J., Hong, I. K., Kim, H. J., Jeong, H. J., Choi, M. J., Yoon, C. N., & Jeong, J. H. (2002). Efficient macrocyclization for cyclicpeptide using solid-phase reaction. Archives of pharmacal research, 25(6), 801-806. https://doi.org/10.1007/BF02976995