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

Research output: Contribution to journalArticle

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

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glycylphenylalanine
Molecular modeling
Opioid Receptors
Scaffolds
Opioid Analgesics
Inhibitory Concentration 50
Nuclear magnetic resonance
Experiments
endomorphin 2
phenylalanine-1-tyrosine

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Endomorphin-2 with a β-turn backbone constraint retains the potent μ-opioid receptor agonist properties. / Tömböly, Csaba; Ballet, Steven; Feytens, Debby; Köver, Katalin E.; Borics, Attila; Lovas, Sándor; Al-Khrasani, Mahmoud; Fürst, Zsuzsanna; Tóth, Géza; Benyhe, Sándor; Tourwé, Dirk.

In: Journal of Medicinal Chemistry, Vol. 51, No. 1, 10.01.2008, p. 173-177.

Research output: Contribution to journalArticle

Tömböly, C, Ballet, S, Feytens, D, Köver, KE, 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, vol. 51, no. 1, pp. 173-177. https://doi.org/10.1021/jm7010222
Tömböly, Csaba ; Ballet, Steven ; Feytens, Debby ; Köver, Katalin E. ; Borics, Attila ; Lovas, Sándor ; Al-Khrasani, Mahmoud ; Fürst, Zsuzsanna ; Tóth, Géza ; Benyhe, Sándor ; Tourwé, Dirk. / Endomorphin-2 with a β-turn backbone constraint retains the potent μ-opioid receptor agonist properties. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 1. pp. 173-177.
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AU - Al-Khrasani, Mahmoud

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