Synthesis and binding activity of endomorphin-1 analogues containing beta-amino acids.
Endomorphin-1 (Tyr-Pro-Trp-PheNH2) has been proposed as the most potent endogenous ligand of the mu-opioid receptors. In this paper, we describe the synthesis of some endomorphin-1 based tetrapeptides in which a residue of the sequence Tyr-Pro-Trp-PheNH2 is replaced by the corresponding beta-isomer. These novel peptides showed different affinities for the opioid receptors labeled with [3H]-DAMGO in rat brain membranes, depending on the beta-amino acid. In particular, the tetrapeptide containing beta-Pro (Tyr-beta-(R)-Pro-Trp-PheNH2) displayed a higher affinity than endogenous endomorphin-1, as revealed by their Ki values (0.33 and 11.1 nM, respectively).
Cardillo
G
G
Dipartimento di Chimica G. Ciamician, Università di Bologna, Italy. cardillo@ciam.unibo.it
Gentilucci
L
L
Melchiorre
P
P
Spampinato
S
S
D000596:Amino Acids / Q000737:chemistry*; D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D008024:Ligands; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D014316:Tritium
D000596:Amino Acids; D000701:Analgesics, Opioid; D008024:Ligands; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-