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

    Research output: Contribution to journalArticleAcademicpeer-review

    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.
    Schaaper, W.M.M. ; Adan, R.A.H. ; Posthuma, T.A. ; Oosterom, J. ; Gispen, W.H. ; Meloen, R.H. / Synthesis of cyclic alpha-MSH peptides. In: Letters in peptide science. 1998 ; Vol. 5, No. 2-3. pp. 205-208.
    @article{1577e5c5467b4091a4c0e722e38eeb93,
    title = "Synthesis of cyclic alpha-MSH peptides",
    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.",
    author = "W.M.M. Schaaper and R.A.H. Adan and T.A. Posthuma and J. Oosterom and W.H. Gispen and R.H. Meloen",
    year = "1998",
    language = "Undefined/Unknown",
    volume = "5",
    pages = "205--208",
    journal = "Letters in peptide science",
    issn = "0929-5666",
    publisher = "Springer Verlag",
    number = "2-3",

    }

    Schaaper, WMM, Adan, RAH, Posthuma, TA, Oosterom, J, Gispen, WH & Meloen, RH 1998, 'Synthesis of cyclic alpha-MSH peptides', Letters in peptide science, vol. 5, no. 2-3, pp. 205-208.

    Synthesis of cyclic alpha-MSH peptides. / Schaaper, W.M.M.; Adan, R.A.H.; Posthuma, T.A.; Oosterom, J.; Gispen, W.H.; Meloen, R.H.

    In: Letters in peptide science, Vol. 5, No. 2-3, 1998, p. 205-208.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Synthesis of cyclic alpha-MSH peptides

    AU - Schaaper, W.M.M.

    AU - Adan, R.A.H.

    AU - Posthuma, T.A.

    AU - Oosterom, J.

    AU - Gispen, W.H.

    AU - Meloen, R.H.

    PY - 1998

    Y1 - 1998

    N2 - 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.

    AB - 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.

    M3 - Article

    VL - 5

    SP - 205

    EP - 208

    JO - Letters in peptide science

    JF - Letters in peptide science

    SN - 0929-5666

    IS - 2-3

    ER -

    Schaaper WMM, Adan RAH, Posthuma TA, Oosterom J, Gispen WH, Meloen RH. Synthesis of cyclic alpha-MSH peptides. Letters in peptide science. 1998;5(2-3):205-208.