The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 and Tyr-Pro-Phe-Phe-NH(2); EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) exhibit an extremely high selectivity for mu-opioid receptor. Here a series of novel EM2 and morphiceptin analogues containing in place of the proline at position 2 the S and R residues of beta-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3-pyrrolidinesulphonic acid (beta Prs) have been synthesized and their binding affinity and functional activity have been investigated. The highest p-receptor affinity is shown by [(S)beta Prs(2)]EM2 analogue (6e) which represents the first example of a beta-sulphonamido analogue in the field of mold peptides. (C) 2010 Elsevier Masson SAS. All rights reserved.
Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2 / Cesare, Giordano; Anna, Sansone; Annalisa, Masi; Lucente, Gino; Punzi, Pasqualina; Adriano, Mollica; Francesco, Pinnen; Federica, Feliciani; Ivana, Cacciatore; Peg, Davis; Josephine, Lai; M. A., Shou Wu; Frank, Porreca; Hruby, Victor. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 45:10(2010), pp. 4594-4600. [10.1016/j.ejmech.2010.07.022]
Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2
LUCENTE, Gino;PUNZI, PASQUALINA;
2010
Abstract
The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 and Tyr-Pro-Phe-Phe-NH(2); EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) exhibit an extremely high selectivity for mu-opioid receptor. Here a series of novel EM2 and morphiceptin analogues containing in place of the proline at position 2 the S and R residues of beta-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3-pyrrolidinesulphonic acid (beta Prs) have been synthesized and their binding affinity and functional activity have been investigated. The highest p-receptor affinity is shown by [(S)beta Prs(2)]EM2 analogue (6e) which represents the first example of a beta-sulphonamido analogue in the field of mold peptides. (C) 2010 Elsevier Masson SAS. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.