Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2.
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.
Giordano
Cesare
C
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
Sansone
Anna
A
Masi
Annalisa
A
Lucente
Gino
G
Punzi
Pasqualina
P
Mollica
Adriano
A
Pinnen
Francesco
F
Feliciani
Federica
F
Cacciatore
Ivana
I
Davis
Peg
P
Lai
Josephine
J
Ma
Shou-Wu
SW
Porreca
Frank
F
Hruby
Victor
V
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
D000701:Analgesics, Opioid; D004723:Endorphins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C105294:endomorphin 2; C028889:morphiceptin; D011392:Proline