title: Hybrid peptides endomorphin-2/DAMGO: design, synthesis and biological evaluation.
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 μ 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 μ-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 μ affinity (Kiμ=34 nM), combined with a remarkable in vivo antinociceptive activity.
authors: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio" di Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy. Electronic address: a.mollica@unich.it.
authors: Adriano
authors: A
authors: Mollica
authors: Roberto
authors: R
authors: Costante
authors: Azzurra
authors: A
authors: Stefanucci
authors: Francesco
authors: F
authors: Pinnen
authors: Grazia
authors: G
authors: Luisi
authors: Stefano
authors: S
authors: Pieretti
authors: Anna
authors: A
authors: Borsodi
authors: Engin
authors: E
authors: Bojnik
authors: Sándor
authors: S
authors: Benyhe
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004795:Enzyme Stability / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists*
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C105294:endomorphin 2
keywords: Analgesics; DAMGO; Endomorphins; Hot plate; Nociception; Opioid; Tail flick