Endomorphin-2 with a β-turn backbone constraint retains the potent μ-opioid receptor agonist properties

Csaba Tömböly, Steven Ballet, Debby Feytens, Katalin E. Köver, Attila Borics, Sándor Lovas, Mahmoud Al-Khrasani, Zsuzsanna Fürst, Géza Tóth, Sándor Benyhe, Dirk Tourwé

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Abstract

The constitutional similarity with different secondary structure preference between the Aba-Gly and the spiro-Aba-Gly scaffolds were exploited to design the novel endomorphin-2 analogs Tyr-spiro-(R/S)-Aba-Gly-Phe-NH2 (1 and 2) and Tyr-(R/S)-Aba-Gly-Phe-NH2 (3 and 4). The (R)-spiro analog 1 was found to be a potent and selective μ-opioid agonist/partial agonist (K = 29.3 nM, IC50 = 50 nM, Ke = 0.57). NMR experiments and molecular modeling indicated that its backbone adopts mainly a β-turn in aqueous solution.

Original languageEnglish (US)
Pages (from-to)173-177
Number of pages5
JournalJournal of Medicinal Chemistry
Volume51
Issue number1
DOIs
StatePublished - Jan 10 2008

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Tömböly, C., Ballet, S., Feytens, D., Köver, K. E., Borics, A., Lovas, S., Al-Khrasani, M., Fürst, Z., Tóth, G., Benyhe, S., & Tourwé, D. (2008). Endomorphin-2 with a β-turn backbone constraint retains the potent μ-opioid receptor agonist properties. Journal of Medicinal Chemistry, 51(1), 173-177. https://doi.org/10.1021/jm7010222