Conformationally restricted analogs of somatostatin with high mu-opiate receptor specificity.
A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5] [3H]enkephalin to rat brain membranes. The most potent analog, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 where Pen is penicillamine in [D-Phe5, Cys6, Tyr7, D-Trp8, Pen11]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for mu-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high mu-opiate receptor selectivity with an IC50 [( D-Ala2,D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for mu-opiate receptors may be of use in examining the physiological role(s) of the mu-opiate receptor.
Pelton
J T
JT
Gulya
K
K
Hruby
V J
VJ
Duckles
S P
SP
Yamamura
H I
HI
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D006728:Hormones; D009270:Naloxone / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism
D006728:Hormones; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D013004:Somatostatin; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine