873684-50-5Relevant academic research and scientific papers
Novel Cyclic Biphalin Analogues by Ruthenium-Catalyzed Ring Closing Metathesis: In Vivo and in Vitro Biological Profile
Stefanucci, Azzurra,Lei, Wei,Pieretti, Stefano,Dimmito, Marilisa Pia,Luisi, Grazia,Novellino, Ettore,Nowakowski, Micha,Ko?miński, Wiktor,Mirzaie, Sako,Zengin, Gokhan,Streicher, John M.,Mollica, Adriano
, p. 450 - 456 (2019)
In this work we report the application of the ring-closing metathesis (RCM) to the preparation of two cyclic olefin-bridged analogues of biphalin (Tyr-d-Ala-Gly-Phe-NH-NH a Phe a Gly a d-Ala a Tyr), using the second generation Grubbs' catalyst. The resulting cis- and trans-cyclic isomers were identified, fully characterized, and tested in vitro at μ (IR), ? (DOR), and ?° (KOR) opioid receptors and in vivo for antinociceptive activity. Both were shown to be full agonists at MOR and potential partial antagonists at DOR, with low potency KOR agonism. They also share a strong antinociceptive effect after intracerebroventricular (i.c.v.) and intravenous (i.v.) administration, higher than that of the cyclic biphalin analogues containing a disulfide bridge between the side chains of two d-Cys or d-Pen residues, previously described by our group.
Cyclic Biphalin Analogues Incorporating a Xylene Bridge: Synthesis, Characterization, and Biological Profile
Stefanucci, Azzurra,Carotenuto, Alfonso,Macedonio, Giorgia,Novellino, Ettore,Pieretti, Stefano,Marzoli, Francesca,Szücs, Edina,Erdei, Anna I.,Zádor, Ferenc,Benyhe, Sándor,Mollica, Adriano
, p. 858 - 863 (2017/08/16)
In this work we enhanced the ring lipophilicity of biphalin introducing a xylene moiety, thus obtaining three cyclic regioisomers. Novel compounds have similar in vitro activity as the parent compound, but one of these (6a) shows a remarkable increase of in vivo antinociceptive effect. Nociception tests have disclosed its significant high potency and the more prolonged effect in eliciting analgesia, higher than that of biphalin and of the disulfide-bridge-containing analogue (7).
Novel cyclic biphalin analogue with improved antinociceptive properties
Mollica, Adriano,Carotenuto, Alfonso,Novellino, Ettore,Limatola, Antonio,Costante, Roberto,Pinnen, Francesco,Stefanucci, Azzurra,Pieretti, Stefano,Borsodi, Anna,Samavati, Reza,Zador, Ferenc,Benyhe, Sndor,Davis, Peg,Porreca, Frank,Hruby, Victor J.
supporting information, p. 1032 - 1036 (2014/12/10)
Two novel opioid analogues have been designed by substituting the native d-Ala residues in position 2,2′ of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent μ/δ mixed receptor affinities (Kiδ = 5.2 nM; Kiμ = 1.9 nM), together with an efficacious capacity to trigger the second messenger and a very good in vivo antinociceptive activity, whereas product 10 was scarcely active. An explanation of the two different pharmacological behaviors of products 9 and 10 was found by studying their conformational properties.
Biological active analogues of the opioid peptide biphalin: Mixed α/β3-peptides
Mollica, Adriano,Pinnen, Francesco,Costante, Roberto,Locatelli, Marcello,Stefanucci, Azzurra,Pieretti, Stefano,Davis, Peg,Lai, Josephine,Rankin, David,Porreca, Frank,Hruby, Victor J.
, p. 3419 - 3423 (2013/06/05)
Natural residues of the dimeric opioid peptide Biphalin were replaced by the corresponding homo-β3 amino acids. The derivative 1 containing hβ3 Phe in place of Phe showed good μ- and δ-receptor affinities (Kiδ =
