[D-Ala2]deltorphin II analogs with high affinity and selectivity for delta-opioid receptor.
Nine [D-Ala2]deltorphin II (DL-II:Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2) analogs having various aliphatic amino acids at positions 5 and 6 were synthesized to gain more information about the role of hydrophobic Val5,6 residues for the delta-opioid receptor selectivity. Binding assays of analogs replaced by Ala demonstrated the importance of hydrophobic Val5,6 residues in DL-II for delta-affinity and selectivity, and especially critical importance of Val5 residue for higher delta-selectivity. By enhancing the hydrophobicity of residues at positions 5 and 6, we have developed analogs with very high delta-affinity and selectivity over those of DL-II, e.g., [Ile5,6], [norleucine5,6] and [gamma-methyl-leucine5,6]DL-II, which will be useful as delta-selective ligands for investigation of the physiological role of opioid receptors.
Sasaki
Y
Y
Tohoku College of Pharmacy, Sendai, Japan.
Ambo
A
A
Suzuki
K
K
D000818:Animals; D001921:Brain / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism*
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; D016308:Enkephalin, Leucine-2-Alanine