Synthesis of cyclic alpha-MSH peptides

W.M.M. Schaaper, R.A.H. Adan, T.A. Posthuma, J. Oosterom, W.H. Gispen, R.H. Meloen

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    Abstract

    Cyclic lactam analogs of α-melanocyte stimulating hormone (α-MSH) have been shown to be potent agonists in the frog skin bioassay [Al-Obeidi, F. et al., J. Med. Chem., 32 (1989) 2555], demonstrating melanocortin-1 (MC1) receptor activity. We synthesized cyclic α-MSH(1-13) and α-MSH(4-10) lactam analogs. The peptides were synthesized using Fmoc chemistry. We improved the cyclization procedure: side chains of Asp5 and Lys10 from the deprotected peptide were coupled in DMF to form a cyclic lactam, using an excess of PyBOP reagent and DIEA as a base. The cyclization reaction was completed within 1 h and was almost quantitative. We also synthesized an α-MSH analog cyclized via a disulphide bridge. The peptides were tested for their selectivity for the rat MC4 receptor. Cyclization and substitutions at position 7 dramatically influenced the selectivity for the rMC4 receptor.
    Original languageUndefined/Unknown
    Pages (from-to)205-208
    JournalLetters in peptide science
    Volume5
    Issue number2-3
    Publication statusPublished - 1998

    Cite this

    Schaaper, W. M. M., Adan, R. A. H., Posthuma, T. A., Oosterom, J., Gispen, W. H., & Meloen, R. H. (1998). Synthesis of cyclic alpha-MSH peptides. Letters in peptide science, 5(2-3), 205-208.