Endomorphin-2 with a β-Turn Backbone Constraint Retains the Potent μ-Opioid Receptor Agonist Properties

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• 作者：Csaba Tö ; mbö ; ly ; Steven Ballet ; Debby Feytens ; Katalin E. Kö ; vé ; r ; Attila Borics ; Sá ; ndor Lovas ; Mahmoud Al-Khrasani ; Zsuzsanna Fü ; rst ; Gé ; za Tó ; th ; Sá ; ndor Benyhe
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：January 10, 2008
• 年：2008
• 卷：51
• 期：1
• 页码：173 - 177
• 全文大小：287K
• 年卷期：v.51,no.1(January 10, 2008)
• ISSN：1520-4804

文摘

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_iμ = 29.3 nM, IC₅₀ = 50 nM, K_e = 0.57). NMR experiments and molecular modeling indicated that its backbone adopts mainly a β-turn in aqueous solution.