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Synthesis of the diastereomers of β-Me-Tyr and β-Me-Phe and their effect on the biological properties of the delta opioid receptor antagonist TIPP

  • Section II. Synthesis and Libraries
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Summary

In order to influence side-chain conformations and to increase the μ-agonist properties of the δ-selective opioid receptor δ-antagonist H-Tyr-Tic-Phe-Phe-NH2, residues Tyr1, Phe3 and Phe4 were replaced by their β-methyl-substituted stereoisomers. Synthesis of β-Me-Tyr was carried out in a stereoselective way. Incorporation of the modified amino acids was performed by SPPS. Receptor binding data and GPI and MVD bioassays were obtained for all stereoisomers, in general showing equal or slightly increased potencies. In the [(R,S)β-Me-Phe3]analogue, the introduction of the β-methyl substituent restores signal transduction.

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Authors and Affiliations

  1. Organic Chemistry, Free University of Brussels, Pleinlaan 2, B-1050, Brussels, Belgium

    Els Mannekens, Dirk Tourwé, Sylvia Vanderstichele & Trang Nguyen Thi Diem

  2. Biological Research Center, H-6701, Szeged, Hungary

    Géza Tóth & Antal Péter

  3. A. Jozsef University, H-6701, Szeged, Hungary

    Géza Tóth & Antal Péter

  4. Clinical Research Institute of Montreal, H2W 1R7, Montreal, PQ, Canada

    Nga N. Chung & Peter W. Schiller

Authors
  1. Els Mannekens
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  2. Dirk Tourwé
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  3. Sylvia Vanderstichele
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  4. Trang Nguyen Thi Diem
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  5. Géza Tóth
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  6. Antal Péter
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  7. Nga N. Chung
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  8. Peter W. Schiller
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Mannekens, E., Tourwé, D., Vanderstichele, S. et al. Synthesis of the diastereomers of β-Me-Tyr and β-Me-Phe and their effect on the biological properties of the delta opioid receptor antagonist TIPP. Lett Pept Sci 2, 190–192 (1995). https://doi.org/10.1007/BF00119150

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  • DOI: https://doi.org/10.1007/BF00119150

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