Hybrid peptides endomophin-2/DAMGO: Design, synthesis and biological evaluation

Mollica, Adriano and Costante, Roberto and Stefanucci, Azzurra and Borsodi, Anna and Bojnik, Engin and Benyhe, Sándor (2013) Hybrid peptides endomophin-2/DAMGO: Design, synthesis and biological evaluation. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 68 (2013). pp. 167-177. ISSN 0223-5234

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Abstract

Endomorphin-2 [Tyr-Pro-Phe-Phe-NH2] and DAMGO [Tyr-D-Ala-Gly-(N-Me)Phe-Gly-ol] are natural (EM2) and synthetic (DAMGO) opioid peptides both selective for mu opioid receptor with high analgesic activity. In this work we report synthesis, in vitro and in vivo biological evaluation of five new hybrid EM2/DAMGO analogues, with the aim to obtain compounds with high affinity at mu-opioid receptor, high activity in animal nociception tests (hot plate and tail flick) and improved enzymatic stability. Double N-methylation on both Phe residues and C-terminal ethanolamide led to analogue 6e, which possesses a good in vitro mu affinity (Kimu = 34 nM), combined with a remarkable in vivo antinociceptive activity.

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