title: Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2.
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 (betaPrs) have been synthesized and their binding affinity and functional activity have been investigated. The highest micro-receptor affinity is shown by [(S)betaPrs(2)]EM2 analogue (6e) which represents the first example of a beta-sulphonamido analogue in the field of opioid peptides.
authors.affiliation: Istituto di Chimica Biomolecolare del CNR, c/o Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185 Roma, Italy. cesare.giordano@uniroma1.it
authors.forename: Cesare
authors.initials: C
authors.lastname: Giordano
authors.forename: Anna
authors.initials: A
authors.lastname: Sansone
authors.forename: Annalisa
authors.initials: A
authors.lastname: Masi
authors.forename: Gino
authors.initials: G
authors.lastname: Lucente
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Punzi
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.forename: Francesco
authors.initials: F
authors.lastname: Pinnen
authors.forename: Federica
authors.initials: F
authors.lastname: Feliciani
authors.forename: Ivana
authors.initials: I
authors.lastname: Cacciatore
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.forename: Shou-Wu
authors.initials: SW
authors.lastname: Ma
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Victor
authors.initials: V
authors.lastname: Hruby
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004723:Endorphins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D004723:Endorphins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C105294:endomorphin 2; C028889:morphiceptin; D011392:Proline