[3H]DSTBULET, a new linear hexapeptide with both an improved selectivity and a high affinity for delta-opioid receptors.
The binding properties of the new agonist Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr, DSTBULET, in rat brain tissue shows that insertion of a bulky t.butyl group into the sequence of DSLET leads to a conformationally-induced large increase in selectivity for delta opioid receptors (KI(delta)/KI(mu) = 0.012). In addition to its similar selectivity to that of the cyclic enkephalins DPDPE and DPLPE, the affinity of [3H]DSTBULET for delta sites (KD = 2.9 nM) is significantly better than that of [3H]DPDPE (KD approximately 10.5 nM) or DPLPE (KI (delta) approximately 19 nM). DSTBULET is therefore the most appropriate probe for both binding studies and pharmacological investigations of delta-receptors as illustrated by a comparison of the analgesic properties of DAGO, DSTBULET and DPLPE.
Delay-Goyet
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P
Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté de Pharmacie, Paris.
Seguin
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C
Daugé
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Calenco
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Morgat
J L
JL
Gacel
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G
Roques
B P
BP
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007700:Kinetics; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D013329:Structure-Activity Relationship
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C054868:tyrosyl-seryl(O-tert-butyl)-glycyl-phenylalanyl-leucyl-threonine; D020881:Enkephalin, D-Penicillamine (2,5)-